Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.65936233
DNMT 1 has been shown to have a preference for hemimethylated DNA and has therefore been termed the maintenance methyltransferase . 0.65936233^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Embryonic stem ( ES ) cells homozygous for a disruption of the DNA ( cytosine 5 ) methyltransferase gene ( Dnmt ) proliferate normally with their DNA highly demethylated but die upon differentiation . ^^^ Expression of the wild type Dnmt cDNA in mutant male ES cells caused an increase in methylation of bulk DNA and of the Xist and Igf 2 genes to normal levels , but did not restore the methylation of the imprinted genes H 19 and Igf2r . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Xist and other 10 linked gene expression was examined by fluorescence in situ hybridization in cells of wild type and DNA methyltranferase ( Dnmt ) mutant embryos and embryonic stem ( ES ) cells to determine whether demethylation induced Xist expression leads to inappropriate 10 chromosome inactivation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Previous attempts to express functional DNA cytosine methyltransferase ( EC 2 . 1 . 1 . 37 ) in cells transfected with the available Dnmt cDNAs have met with little or no success . ^^^ This was shown by functional rescue of Dnmt mutant embryonic stem cells that contain highly demethylated genomic DNA and fail to differentiate normally . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
These data suggest that any sequence specific de novo methylation mediated by Dnmt 1 is either under the control of regulatory factors that interact with Dnmt 1 , or is cued by alternative secondary structures in DNA . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA ( cytosine 5 ) methyltransferase ( MCMT ) methylates newly replicated mammalian DNA , but the factors regulating this activity are unknown . ^^^ Here , MCMT is shown to bind proliferating cell nuclear antigen ( PCNA ) , an auxiliary factor for DNA replication and repair . ^^^ Binding of PCNA requires amino acids 163 to 174 of MCMT , occurs in intact cells at foci of newly replicated DNA , and does not alter MCMT activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Trace levels of 5 methylcytosine persist in the DNA of mouse embryonic stem cells that are homozygous for null mutations in Dnmt 1 , the gene for the one previously recognized metazoan DNA methyltransferase . ^^^ Dnmt 2 is more similar to a putative DNA methyltransferase of the fission yeast Schizosaccharomyces pombe than to Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The mRNA for Dnmt 1 , the predominant maintenance and de novo DNA ( cytosine 5 ) methyl transferase in mammals , is present at high levels in postmitotic murine germ cells but undergoes alternative splicing of sex specific 5 ' exons , which controls the production and localization of enzyme during specific stages of gametogenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have shown previously that de novo methylation activities persist in mouse embryonic stem ( ES ) cells homozygous for a null mutation of Dnmt 1 that encodes the major DNA cytosine methyltransferase . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Two recent reports have identified DNA ( cytosine 5 ) methyltransferase ( MCMT ) and the DNA repair endonuclease XPG as binding to PCNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we report that murine embryonic stem cells nullizygous for the major DNA methyltransferase ( Dnmt 1 ) gene exhibited significantly elevated mutation rates at both the endogenous hypoxanthine phosphoribosyltransferase ( Hprt ) gene and an integrated viral thymidine kinase ( tk ) transgene . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We found , by representational difference analysis , that expression of DNA 5 methylcytosine transferase ( dnmt 1 ) in fos transformed cells is three times the expression in normal fibroblasts and that fos transformed cells contain about 20 percent more 5 methylcytosine than normal fibroblasts . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Identification of initiation sites for DNA replication in the human dnmt 1 ( DNA methyltransferase ) locus . ^^^ Dnmt 1 encodes the maintenance enzyme DNA methyltransferase , which is responsible for propagating the DNA methylation pattern and the epigenetic information that it encodes during replication . ^^^ Direct sequence analysis and bisulfite mapping of the 5 ' region of DNA methyltransferase 1 ( dnmt 1 ) have indicated the presence of many sequence elements associated with previously characterized origins of DNA replication . ^^^ Based on these lines of evidence , we propose that initiation sites for DNA replication are located between the first intron and exon 7 of the human dnmt 1 locus . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Triple helix formation of DNA oligomers with methylthiourea linked nucleosides ( DNmt ) : a kinetic and thermodynamic analysis . ^^^ The melting temperatures , Tm , the association and dissociation kinetic and thermodynamic parameters , and activation energies were determined by UV thermal analysis for the triplexes of short strand DNA homooligomers [ d ( pA ) 10 d ( pA ) 23 ] and poly ( dA ) with the methylthiourea linked nucleoside [ 5 ' NH3+ d ( Tmt ) 4 T OH [ DNmt 5 ] ] . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
RNA and protein levels of the DNA methyltransferase DNMT 1 have been shown to be elevated in tumors , however murine stem cells lacking Dnmt 1 are still able to de novo methylate viral DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The encoded proteins differ from the predominant mammalian DNA methyltransferase DNMT 1 in that they have a substantially higher ratio of de novo to maintenance methyltransferase activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase gene ( dnmt 1 ) encodes the enzyme catalyzing the methylation of DNA during replication . ^^^ We show that DNA methyltransferase ( Dnmt 1 ) activity is sharply reduced 4 days after induction of differentiation of PC 12 cells with NGF . ^^^ We propose that the level of Dnmt 1 is downregulated to adjust the activity of the DNA methyltransferase to a different role in mature post mitotic neurons . ^^^ The temporal pattern of downregulation of dnmt 1 in nerve growth factor ( NGF ) induced PC 12 cells is different from myotube differentiation where downregulation of DNA methyltransferase and demethylation is an early event and was proposed to play a causal role in differentiation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNMT 1 is constitutively expressed and is required for the maintenance of global methylation after DNA replication . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
This paper tests the hypothesis that expression of the DNA methyltransferase , dnmt 1 , gene is regulated by a methylation sensitive DNA element . ^^^ Global inhibition of DNA methylation in P 19 cells by 5 azadeoxycytidine results in demethylation of the AP 1 regulatory region and induction of dnmt 1 expression in P19cells , but not Y 1 cells . ^^^ We propose that this regulatory region of dnmt 1 acts as a sensor of the DNA methylation capacity of the cell . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The role of the maintenance DNA methyltransferase ( DNMT 1 ) in the acquisition of such abnormal CpG dinucleotide methylation changes in colorectal cancer cells remains controversial ; in one study , 60 200 fold increases in DNMT 1 mRNA expression were detected in colorectal polyps and cancers relative to normal colonic tissue [ W . ^^^ A concordance of DNMT 1 expression with the expression of PCNA and other cell proliferation markers , such as Ki 67 and DNA topoisomerase IIalpha , was observed in normal colonic epithelial cells and in cells comprising other normal epithelia and lymphoid tissues . ^^^ The polypeptide p 21 , which has been reported to undermine DNMT 1 binding to proliferating cell nuclear antigen at DNA replication sites , was not expressed by normal colonic cells containing DNMT 1 and other cell proliferation markers . ^^^ These results indicate that human colorectal carcinogenesis is accompanied by a progressive dysregulation of DNMT 1 expression and suggest that abnormalities in DNMT 1 expression may contribute to the abnormal CpG dinucleotide methylation changes characteristic of human colorectal carcinoma cell DNA . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Furthermore , we have addressed the question of a requirement for DNA methylation for the Mash 2 imprinting mechanism by crossing our Mash 2 lacZ mice with mice mutant for Dnmt 1 ( DNA methyltransferase 1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The overall DNA methylation level sharply decreases from the zygote to the blastocyst stage despite the presence of high levels of DNA methyltransferase ( Dnmt 1 ) . ^^^ Altogether , our results suggest that Dnmt 1 is actively retained in the cytoplasm , which prevents binding to its DNA substrate in the nucleus and thereby contributes to the erasure of gamete specific epigenetic information during early mammalian development . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The enzymatic properties of the molecule are similar to those of Dnmt 1 methyltransferases isolated from other organisms , but with the peculiarity to be unable to make ' de novo ' methylation on double stranded DNA . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A method is described to express and purify human DNA ( cytosine 5 ) methyltransferase ( human DNMT 1 ) using a protein splicing ( intein ) fusion partner in a baculovirus expression vector . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Initial velocity determinations were conducted with human DNA ( cytosine 5 ) methyltransferase ( DNMT 1 ) on unmethylated and hemimethylated DNA templates in order to assess the mechanism of the reaction . ^^^ Velocity equations indicated a two step mechanism as follows : first , activation of DNMT 1 by methylated DNA that bound to an allosteric site , and second , the addition of AdoMet and DNA to the catalytic site . ^^^ The preference of DNMT 1 for hemimethylated DNA may be the result of positive cooperativity of AdoMet binding mediated by allosteric activation by the methylated CG steps . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation appears to be critical for mammalian development because mice nullizygous for a targeted disruption of the DNMT 1 DNA methyltransferase die at an early embryonic stage . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase Dnmt 1 associates with histone deacetylase activity . ^^^ The DNA methyltransferase Dnmt 1 is responsible for cytosine methylation in mammals and has a role in gene silencing . ^^^ We suggest that the process of DNA methylation , mediated by Dnmt 1 , may depend on or generate an altered chromatin state via histone deacetylase activity . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The mammalian DNA cytosine C 5 methyltransferase Dnmt 1 shows an even more pronounced partitioning toward product formation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Structural properties of hybrid triplex of polycation deoxyribonucleic S methylthiourea ( DNmt ) strands with a complementary DNA strand , probed by nanosecond molecular dynamics . ^^^ The replacement of phosphodiester linkages of the polyanion DNA with S methylthiourea linkers provides the polycation deoxyribonucleic S methylthiourea ( DNmt ) . ^^^ Molecular dynamics studies to 1 , 220 ps of the hybrid triplex formed from octameric DNmt strands d ( Tmt ) 8 with a complementary DNA oligomer strand d ( Ap ) 8 have been carried out with explicit water solvent and Na+Cl counterions under periodic boundary conditions using the CHARMM force field and the Ewald summation method . ^^^ The dynamic structures of the DNmt 10 DNA 10 DNmt triplex were determined by examining histograms from the last 800 ps of the dynamics run . ^^^ The sugar pseudorotation phase angles and the ring rotation angles for the DNA strand are within the C3 ' endo domain and C2 ' endo domain for the DNmt strand . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In mouse , this DNA ( cytosine 5 ) methyltransferase , or CpG MTase , is encoded by the Dnmt 1 gene . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Structure and function of the mouse DNA methyltransferase gene : Dnmt 1 shows a tripartite structure . ^^^ Dnmt 1 is the predominant DNA methyltransferase ( MTase ) in mammals . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Transcriptional regulation of the human DNA Methyltransferase ( dnmt 1 ) gene . ^^^ Understanding the regulation of the DNA Methyltransferase ( dnmt 1 ) gene expression is critical for comprehending how DNA methylation is coordinated with other critical biological processes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The generation and proper maintenance of DNA methylation patterns are essential for embryonic development , as demonstrated by the lethal phenotypes of mice with either a targeted disruption of Dnmt 1 , the gene responsible for the maintenance of DNA methylation , or targeted disruption of Dnmt3a or Dnmt3b , the genes involved in generation of newly formed methylation patterns . ^^^ Dnmt1b protein purified from a baculovirus expression system was demonstrated to be a functional DNA methyltransferase , and to have Michaelis constants for both DNA and S adenosyl L methionine similar to baculovirus expressed Dnmt 1 . ^^^ However , antibodies raised against Dnmt1b epitopes demonstrated that Dnmt1b protein was present at approximately 2 5 % of the level of Dnmt 1 and therefore represents only a minor DNA methyltransferase isoform in human cells . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
However , [ ( 3 ) H ] methyl group incorporation into DNA increased significantly in wild type mice after reperfusion , but not in mutant mice heterozygous for a DNA methyltransferase gene deletion ( Dnmt ( S / + ) ) . ^^^ Dnmt ( S / + ) mice were resistant to mild ischemic damage , suggesting that increased DNA methylation is associated with augmented brain injury after MCA occlusion . ^^^ In contrast to mild stroke , however , DNA methylation was not enhanced , and reduced dnmt gene expression was not protective in an ischemia model of excitotoxic / necrotic cell death . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Solid phase synthesis of oligomeric deoxynucleic thiourea ( DNT ) and deoxynucleic S methylthiourea ( DNmt ) : a neutral / polycationic analogue of DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The mouse ( cytosine 5 ) DNA methyltransferase ( Dnmt 1 ) consists of a regulatory N terminal and a catalytic C terminal domain , which are fused by a stretch of Gly Lys dipeptide repeats . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The prototypic DNA methyltransferase , DNMT 1 , has been widely assumed to be responsible for most of the methylation of the human genome , including the abnormal methylation found in cancers . ^^^ Here we show that cells lacking DNMT 1 exhibited markedly decreased cellular DNA methyltransferase activity , but there was only a 20 % decrease in overall genomic methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It is unlikely that biallelic expression of H 19 following culture in Whitten ' s medium is a generalized effect of lower methylation levels , since the amount of DNA methyltransferase activity and the spatial distribution of Dnmt 1 protein were similar in in vivo derived and cultured embryos . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To test whether demethylation of the kappa locus can activate recombination , we generated two recombinationally active B cell lines in which the gene for maintenance of genomic DNA methylation , Dnmt 1 , was flanked with loxP sites . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We show here that the chief enzyme that maintains mammalian DNA methylation , DNMT 1 , can also establish a repressive transcription complex . ^^^ Thus , DNMT 1 not only maintains DNA methylation , but also may directly target , in a heritable manner , transcriptionally repressive chromatin to the genome during DNA replication . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we show that the predominant mammalian DNA methyltransferase , DNMT 1 , co purifies with the retinoblastoma ( Rb ) tumour suppressor gene product , E2F1 , and HDAC 1 and that DNMT 1 cooperates with Rb to repress transcription from promoters containing E2F binding sites . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Aberrant expression of DNA methyltransferase 1 ( dnmt 1 ) is a downstream effector of multiple tumorigenic pathways , and several data suggest that dnmt 1 plays a causal role in these pathways . ^^^ It is proposed that DNMT 1 induces cellular transformation by a mechanism that does not involve DNA methylation and that the low level of methylation in cancer cells is a result of induction of a DNA demethylase in these cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have studied the mechanisms and genetic pathways by which a targeted heterozygous deficiency in the murine 5 cytosine DNA methyltransferase gene ( Dnmt 1 ( N / + ) ) diminishes intestinal tumorigenesis in C57BL / 6 multiple intestinal neoplasia ( Min ) / + mice . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Maintenance type DNA methyltransferase ( Dnmt 1 ) is usually down regulated in non proliferating cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
MBD 2 MBD 3 complex binds to hemi methylated DNA and forms a complex containing DNMT 1 at the replication foci in late S phase . ^^^ We hypothesize that the MBD 2 MBD3 complex recognizes hemi methylated DNA concurrent with DNA replication and recruits histone deacetylase complexes , as well as DNMT 1 , to establish and / or maintain the transcriptionally repressed chromatin . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Using DNA methyltransferase 1 ( Dnmt 1 ) deficient mouse embryos carrying 10 linked lacZ transgenes , we studied the effects of genomic demethylation on 10 inactivation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Global genome demethylation caused by targeted mutations in the DNA methyltransferase 1 ( Dnmt 1 ) gene has shown that cytosine methylation plays essential roles in 10 inactivation , genomic imprinting and genome stabilization . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Genome demethylation and chromosome instability could not be related to variations in mRNA amounts of the DNA methyltransferases DNMT 1 , DNMT3A , and DNMT3B and DNA demethylase . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we present evidence that this alternative Dnmt 1 transcript present in testis and skeletal muscle is translated despite the presence of several out of frame upstream ATGs and gives rise to a shorter Dnmt 1 isoform , which could play an active role in the change of DNA methylation patterns during gametogenesis and myogenesis . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The DNA methyltransferase Dnmt 1 , and several methyl CpG binding proteins , MeCP 2 , MBD 2 , and MBD 3 , all associate with histone deacetylase . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA cytosine 5 methyltransferase 1 ( DNMT 1 ) is the enzyme believed to be responsible for maintaining the epigenetic information encoded by DNA methylation patterns . ^^^ The N terminal domain has been postulated to have a regulatory role , and it has been suggested that the mammalian DNMT 1 is a fusion of a prokaryotic methyltransferase and a mammalian DNA binding protein . ^^^ We have previously shown that the hemimethylated substrates utilized here act as DNMT 1 antagonists and inhibit DNA replication . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To define the mechanism through which demethylated cells die , and to establish a paradigm for identifying genes regulated by DNA methylation , we have generated mice with a conditional allele for the maintenance DNA methyltransferase gene Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Over expression of DNMT 1 mRNA was significantly associated with CIMP , whereas the level of DNMT3b mRNA was not associated with CIMP or DNA hypomethylation of peri centromeric satellite regions . ^^^ These data suggest that both over expression of the maintenance DNA methyltransferase DNMT 1 and over expression of a newly identified de novo DNA methyltransferase , DNMT3b , are involved in human carcinogenesis , probably at different stages and through different mechanisms . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( Dnmt 1 ) , the maintenance enzyme for DNA cytosine methylation , is expressed at high levels in the CNS during embryogenesis and after birth . ^^^ Dnmt 1 deficiency in postmitotic neurons neither affected levels of global DNA methylation nor influenced cell survival during postnatal life . ^^^ In contrast , Dnmt 1 deficiency in mitotic CNS precursor cells resulted in DNA hypomethylation in daughter cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We show here that the chromatin structure of c 21 gene is inactive in Y 1 cells and that it could be reconfigured to an active form by either expressing antisense mRNA to DNA methyltransferase 1 ( dnmt 1 ) or an attenuator of Ras protooncogenic signaling hGAP . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Expression of DNA methyltransferases DNMT 1 , 3A , and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia . ^^^ Recently identified new DNA methyltransferase ( DNMT ) genes , DNMT3A and DNMT3B , code for de novo methyltransferases . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
These data suggest that overexpression of DNMT 1 and DNMT3a , DNA hypermethylation on CpG islands , and DNA hypomethylation on pericentromeric satellite regions are early events during hepatocarcinogenesis , and that reduced expression of MBD 4 may play a role in malignant progression of HCC . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The enzyme DNA methyltransferase 1 DNMT 1 is responsible for copying the DNA methylation pattern but other de novo methyltransferase as well as demethylases might also be involved . ^^^ DNMT 1 protein might regulate cell cycle events by mechanisms that are independent of its DNA methylation activity through its multiple protein protein interactions . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Maintenance of genomic methylation patterns in mammalian somatic cells depends on DNA methyltransferase 1 ( Dnmt 1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Demethylation of DNA , using 5 azadC or by introducing a mutation in Dnmt 1 , and inhibition of histone hypoacetylation using trichostatin A further increases reactivation in Xist mutant fibroblasts , indicating a synergistic interaction of 10 chromosome silencing mechanisms . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Steady state kinetic analyses revealed that the methylation reaction of the human DNA ( cytosine 5 ) methyltransferase 1 ( DNMT 1 ) is repressed by the N terminal domain comprising the first 501 amino acids , and that repression is relieved when methylated DNA binds to this region . ^^^ DNMT 1 lacking the first 501 amino acids retains its preference for hemimethylated DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Unexpected effects of a heterozygous dnmt 1 null mutation on age dependent DNA hypomethylation and autoimmunity . ^^^ We examined the effects of a null mutation in DNA methyltransferase 1 ( Dnmt 1 ) , a gene maintaining DNA methylation patterns , on immune aging . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Most recently , also complexes of DNA methyltransferase ( Dnmt 1 ) with transcriptional repressors , DMAP 1 and pRB , have been described providing a direct link to transcriptional regulation and tumor suppression . ^^^ Inactivation of the DNA methyltransferase genes ( Dnmt 1 , 3a , and 3b ) was found to be lethal in mice and several human diseases ( ICF and Rett syndrome ) turned out to be linked to DNA methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The activity of the murine DNA methyltransferase Dnmt 1 is controlled by interaction of the catalytic domain with the N terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA . ^^^ The mammalian DNA methyltransferase Dnmt 1 is responsible for the maintenance of the pattern of DNA methylation in vivo . ^^^ CatD , ZnD and NlsD bind to DNA , demonstrating the existence of three independent DNA binding sites in Dnmt 1 . ^^^ Under the experimental conditions , Dnmt 1 has a strong ( 50 fold ) preference for hemimethylated DNA . ^^^ Dnmt 1 is stimulated to methylate unmodified CpG sites by the addition of fully methylated DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The enzyme catalyzes the methylation of DNA in a distributive manner , suggesting that Dnmt3a and Dnmt 1 may cooperate during de novo methylation of DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The objective of the present study was to investigate the effects 1 ) of two different activation protocols , 2 ) the use of quiescent or nonquiescent donor cells ( G ( 0 ) or G ( 1 ) of the cell cycle ) , and 3 ) passage number of donor cells on the relative abundance ( RA ) of eight specific mRNAs ( DNA methyltransferase , DNMT ; mammalian achaete scute homologue , Mash 2 ; glucose transporter 1 , Glut 1 ; heat shock protein 70 . 1 , Hsp ; desmocollin 2 , Dc 2 ; E cadherin , E cad ; interferon tau , IF ; insulin like growth factor 2 receptor , Igf2r ) in single blastocysts employing a semiquantitative reverse transcription polymerase chain reaction assay . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Rb represses E2F mainly by recruiting chromatin remodeling factors ( histone deacetylases and SWI / SNF complexes ) , the DNA methyltransferase DNMT 1 , and a histone methyltransferase . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We demonstrate that the recently identified DNA methyltransferases , Dnmt3a and Dnmt3b , like DNMT 1 , repress transcription in a methylation independent manner . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The turnover and localization of the enzyme DNA ( cytosine 5 ) methyltransferase ( Dnmt 1 ) were studied during Paracentrotus lividus sea urchin embryo development using antibody preparations against the NH ( 2 ) and COOH terminal regions of the molecule . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Proliferation stage dependent expression of DNA methyltransferase ( Dnmt 1 ) in mouse small intestine . ^^^ In cultured cells , the maintenance type DNA methyltransferase ( Dnmt 1 ) is highly expressed during the proliferation stage . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We examined levels of DNA methyltransferase ( DNMT 1 , DNMT3a , DNMT3b ) and DNA demethylase ( MBD 2 ) mRNA expression by semi quantitative RT PCR . ^^^ There was no clear relation between DNA methylation status of hMLH 1 , p 16 ( INK4a ) , and CDH 1 and the mRNA expression levels of DNMT 1 , DNMT3a , DNMT3b or MBD 2 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Symmetrical methylation and the discovery of a DNA methyltransferase that prefers a hemimethylated substrate , Dnmt 1 ( 4 ) , suggested a mechanism by which specific patterns of methylation in the genome could be maintained . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It is generally accepted that this bimodal pattern of methylation is established during development and is then faithfully inherited through subsequent cell divisions by a maintenance DNA methyltransferase ( DNMT 1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Xenopus eggs express an identical DNA methyltransferase , Dnmt 1 , to somatic cells . ^^^ In mouse , an oocyte specific short isoform of DNA methyltransferase 1 ( Dnmt 1 ) lacking amino terminal 118 amino acid residues exists and plays a crucial role in maintaining the methylation state of imprinted genes during early embryogenesis [ Howell et al . ( 2001 ) Cell 104 , 829 838 ] . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
OBJECTIVE : The aim of this study was to investigate whether expression of the enzymes that catalyze cytosine CpG island methylation , DNA methyltransferases , DNMT 1 , DNMT3a , and DNMT3b is altered in human ovarian cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We report the determination of the full length cDNA sequence corresponding to the zebrafish DNA ( cytosine 5 ) methyltransferase gene , Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A number of DNA methyltransferases ( DNMT ) have been identified and a demethylase has recently been reported . ^^^ DNMT 1 also regulates expression of cell cycle proteins by its other regulatory functions and not through its DNA methylation activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Methylation of mammalian DNA by the DNA methyltransferase enzyme ( dnmt 1 ) at CpG dinucleotide sequences has been recognized as an important epigenetic control mechanism in regulating the expression of cellular genes ( Yen , R . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We hypothesized that histone deacetylases ( HDACs ) and DNA methyltransferases ( DNMTase ) are associated with prostate cancer and we examined the enzyme activity , gene , and protein expression of HDAC 1 and DNMT 1 in cell lines and tissues . ^^^ This is the first report to demonstrate that DNMT 1 and HDAC 1 levels are up regulated in prostate cancer compared to BPH , suggesting their roles in inactivation of various genes , by DNA methylation induced chromatin remodeling , in prostate cancer . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Formation of transcriptional repression complexes such as DNA methyltransferase ( DNMT ) 1 / histone deacetylase ( HDAC ) or methyl CpG binding protein / HDAC is emerging as an important mechanism in silencing a variety of methylated tissue specific and imprinted genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The major DNA methyltransferase ( Dnmt 1 ) is associated with nuclear replication sites during S phase , which is consistent with a role in maintenance methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In addition , we targeted the major DNA methyltransferase gene , Dnmt 1 , to investigate the relative contribution of DNA methylation to these various competing gene inactivation pathways . ^^^ We conclude that Dnmt 1 deficiency and the accompanying genomic DNA hypomethylation result in a reduction of three major pathways of gene inactivation in our model system . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation is important for controlling gene expression and is catalyzed by DNA methyltransferase ( Dnmt 1 ) an enzyme abundant in brain . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A critical role for Dnmt 1 and DNA methylation in T cell development , function , and survival . ^^^ The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt 1 in the epigenetic regulation of developmental stage and cell lineage specific gene expression in vivo is uncertain . ^^^ We conclude that Dnmt 1 and DNA methylation are required for the proper expression of certain genes that define fate and determine function in T cells . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We used mouse embryonic stem ( ES ) cells with systematic gene knockouts for DNA methyltransferases to delineate the roles of DNA methyltransferase 1 ( Dnmt 1 ) and Dnmt3a and 3b in maintaining methylation patterns in the mouse genome . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To date , three enzymes , Dnmt 1 , Dnmt3a , and Dnmt3b , are known to have DNA methyltransferase activity in mouse and human . ^^^ These findings indicate that , unlike Dnmt 1 , Dnmt3a most likely methylates one strand of DNA without concurrent methylation of the CpG site on the complementary strand . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The global level of DNA methylation is generally lower ; however , DNA methyltransferase ( Dnmt 1 ) activity is usually higher in tumor cells than in normal cells . ^^^ HT 29 cells cultured in the absence of selenium had significantly hypomethylated DNA but significantly more Dnmt 1 protein expression than cells cultured in the presence of 1 or 2 micromol / L selenium . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The activities of both de novo ( 3 fold ) and maintenance DNA methyltransferases ( DNMT ) ( 5 fold ) were higher in the hepatoma than in the host liver . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The mammalian DNA ( cytosine 5 ) methyltransferase ( Dnmt 1 ) is involved in the maintenance of methylation patterns in the genome during DNA replication and development . ^^^ Overexpression of Rb leads to hypomethylation of the cellular DNA , suggesting that Rb may modulate Dnmt 1 activity during DNA replication in the cell cycle . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The enzymes responsible for CpG methylation are DNA methyltransferase ( DNMT ) 1 , DNMT3a , and DNMT3b , and the enzyme responsible for demethylation is DNA demethylase ( MBD 2 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have compared the intrinsic susceptibilities of the imprinted region of Igf 2 and H 19 , other imprinted genes , bulk genomic DNA , and repetitive retroviral sequences to Dnmt 1 overexpression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We examined the interaction between CpG island hypermethylation and tumorigenesis by genetically modulating expression levels of the predominant DNA methyltransferase , Dnmt 1 , in Apc ( Min / + ) mice . ^^^ These results suggest that sufficient DNA methyltransferase expression is a prerequisite for polyp formation and that hypomorphic alleles of Dnmt 1 are not merely genetic modifiers but the first identified true genetic suppressors of the Min phenotype . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Selective depletion of human DNA methyltransferase DNMT 1 proteins by sulfonate derived methylating agents . 5 Methylcytosine residues in the DNA ( DNA methylation ) are formed from the transfer of the methyl group from S adenosylmethionine to the C 5 position of cytosine by the DNA ( cytosine 5 ) methyltransferases ( DNMTs ) . ^^^ We report here that sulfonate derived methylating agents , unlike N methylnitrosourea or iodomethane , are potent in depleting DNMT 1 proteins in human cells , in addition to their DNA damaging properties . ^^^ Unlike gamma irradiation , these agents apparently do not activate the p53 / p21 ( WAF 1 ) DNA damage response pathway to deplete the DNMT 1 proteins because cells with wild type , mutated , or inactivated p 53 behave similarly . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The C terminal domains of the mammalian DNA methyltransferases Dnmt 1 , Dnmt3a , and Dnmt3b harbor all the conserved motifs characteristic for cytosine C 5 methyltransferases . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The prototypic DNA methyltransferase , Dnmt 1 , accounts for most methylation in mouse cells , but human cancer cells lacking DNMT 1 retain significant genomic methylation and associated gene silencing . ^^^ Surprisingly , however , genetic disruption of both DNMT 1 and DNMT3b nearly eliminated methyltransferase activity , and reduced genomic DNA methylation by greater than 95 % . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have introduced DNA methyltransferase 1 ( Dnmt 1 ) mutations into a mouse strain deficient for the Mlh 1 protein to study the interaction between DNA mismatch repair deficiency and DNA methylation . ^^^ Mice harboring hypomorphic Dnmt 1 mutations showed diminished RNA expression and DNA hypomethylation but developed normally and were tumor free . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Expression of DNA methyltransferase ( Dnmt 1 ) in testicular germ cells during development of mouse embryo . ^^^ In female germ cells , the short form DNA methyltransferase Dnmt 1 , which is an alternative isoform specifically expressed in growing oocytes , plays a crucial role in maintaining imprinted genes . ^^^ To evaluate the contribution of Dnmt 1 to the DNA methylation in male germ cells , the expression profiles of Dnmt 1 in embryonic gonocytes were investigated . ^^^ Inversely , genome wide DNA methylation occurred after germ cell proliferation was arrested , when the Dnmt 1 expression was downregulated . ^^^ The present results indicate that not Dnmt 1 but some other type of DNA methyltransferase contributes to the creation of DNA methylation patterns in male germ cells . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase ( DNMT ) 1 and DNMT3b3 proteins were undetectable in 5 Aza 2 ' deoxycytidine treated and untreated nondividing cells , and their mRNA transcripts were down regulated in these cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dnmt1o is a variant form of the somatically expressed Dnmt 1 cytosine methyltransferase that is synthesized and stored in the oocyte cytoplasm and trafficks to the eight cell nucleus during preimplantation development , where it maintains DNA methylation patterns on alleles of imprinted genes . ^^^ The highly restricted nuclear localization patterns of oocyte derived Dnmt1o and Dnmt 1 during preimplantation development add further support to the notion that DNA methyltransferases other than Dnmt 1 are required for maintaining imprints during preimplantation development . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The observation of persistent methylation in human cancer cells lacking the maintenance methyltransferase DNMT 1 suggests the involvement of other DNA methyltransferases in gene silencing in cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Provirus DNA from infected wild type ( J 1 ) , Dnmt 1 / ( c / c ) , and Dnmt3a3b / ( 3a3b / ) ES cells were analyzed using the bisulfite sequencing method . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Methylation of 5 ' CpG islands of tumor suppressor genes and elevated levels of the DNA ( cytosine 5 ) methyltransferase enzymes ( DNMT 1 , 3A and 3B ) are also prevalent features of human neoplasia . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p 21 ( WAF 1 ) protein demonstrating a regulatory link between DNMT and p 21 ( WAF 1 ) which is independent of methylation of DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this study , we characterized the GC rich promoter of the gene for the DNA methyltransferase ( Dnmt 1 ) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A large body of data point toward 5 cytosine DNA methyltransferase 1 ( DNMT 1 ) as a critical component of oncogenic programs . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Three different families of DNA ( cytosine 5 ) methyltransferases , DNMT 1 , DUMT 2 , DNMT3a and DNMT3b , participate in establishing and maintaining genomic methylation patterns during mammalian development . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we show in L 929 mouse fibroblast cells that inhibition of poly ( ADP ribose ) polymerase ( s ) at different cell cycle phases increases the mRNA and protein levels of the major maintenance DNA methyltransferase ( DNMT 1 ) in G1 / S border . ^^^ Increase of DNMT 1 results in a premature PCNA DNMT 1 complex formation , which facilitates robust maintenance , as well as de novo DNA methylation processes during the G1 / S border , which leads to abnormal hypermethylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Previously , we found that Dnmt 1 knockout embryonic stem ( ES ) cells are capable of methylating retroviral DNA de novo . ^^^ Additionally , biochemical analysis revealed that , unlike Dnmt 1 , neither Dnmt3a nor Dnmt3b had a strong preference to hemimethylated DNA substrates . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Sperm and oocyte genomic methylation patterns depend on the activity of DNA methyltransferases ( Dnmt ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
No relationship was observed between global genomic 5 methylcytosine levels and relative amounts of RNA for DNA methyltransferases DNMT 1 , DNMT3A , and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA cytosine methyltransferase 1 ( Dnmt 1 ) , which preserves epigenetic signals by completing the methylation of hemimethylated DNA after DNA replication , has been indicated as one of these PCNA binding proteins by a previous work . ^^^ The affinity of Dnmt 1 for DNA is much higher for DNA bound by PCNA than for free DNA . ^^^ Furthermore , DNA methylation assays with hemimethylated DNA as a substrate revealed that PCNA clamp bound DNA is methylated more efficiently by Dnmt 1 than is free DNA . ^^^ CONCLUSION : These results provide the first biochemical evidence that physical interactions between PCNA and Dnmt 1 facilitate the methylation of newly neplicated DNA , on which PCNA remains associated as a functional clamp . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dnmt3a and Dnmt 1 functionally cooperate during de novo methylation of DNA . ^^^ In contrast Dnmt 1 shows high preference for hemimethylated DNA . ^^^ However , Dnmt 1 can be activated for the methylation of unmodified DNA . ^^^ We show here that the Dnmt3a and Dnmt 1 DNA methyltransferases functionally cooperate in de novo methylation of DNA , because a fivefold stimulation of methylation activity is observed if both enzymes are present . ^^^ Stimulation is observed if Dnmt3a is used before Dnmt 1 , but not if incubation with Dnmt 1 precedes Dnmt3a , demonstrating that methylation of the DNA by Dnmt3a stimulates Dnmt 1 and that no physical interaction of Dnmt 1 and Dnmt3a is required . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Inhibitors of DNA methyltransferase ( Dnmt ) and histone deacetylases ( HDAC ) synergistically activate the methylated metallothionein 1 gene ( MT 1 ) promoter in mouse lymphosarcoma cells . ^^^ Among the DNA methyltransferases , both Dnmt 1 and Dnmt3a were associated with the MT 1 promoter in the lymphosarcoma cells , and association of Dnmt 1 decreased with time after treatment with 5 AzaC . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In addition , re expression of RII by FTI was associated with a decrease in DNA methyltransferase 1 ( DNMT 1 ) levels . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
This hypomethylation is found in both colorectal cancers and normal mucosa from the same patients , and in cell lines with somatic cell knockout of DNA methyltransferases DNMT 1 and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We report the determination of zebrafish DNA ( cytosine 5 ) methyltransferase ( dnmt 1 ) temporal and spatial patterns of expression in gonadal tissues and during early development . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferases , DNMT 1 and 3 ( 3a and 3b ) , have been implicated in mediating maintenance and de novo methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Methyl CpG binding protein , MeCP 2 , is a target molecule for maintenance DNA methyltransferase , Dnmt 1 . ^^^ Here we show that the methyl CpG binding protein , MeCP 2 , interacts directly with the maintenance DNA methyltransferase , Dnmt 1 . ^^^ We propose that genome wide and / or specific local DNA methylation may be maintained by the Dnmt 1 MeCP2 complexes , bound to hemimethylated DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The major DNA cytosine methyltransferase isoform in mouse erythroleukemia cells , Dnmt 1 , exhibits potent dead end inhibition with a single stranded nucleic acid by binding to an allosteric site on the enzyme . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Genetic experiments have defined the importance of the DNA methyltransferase Dnmt 1 for the maintenance of methylation in mouse cells and its role in neoplasia . ^^^ In contrast , targeted disruption of DNMT 1 alleles in HCT 116 human colon cancer cells produced clones that retained CpG island methylation and associated tumor suppressor gene silencing , whereas HCT 116 clones with inactivation of both DNMT 1 and DNMT3B showed much lower levels of DNA methylation , suggesting that the two enzymes are highly cooperative . ^^^ We used a combination of genetic ( antisense and siRNA ) and pharmacologic ( 5 aza 2 ' deoxycytidine ) inhibitors of DNA methyl transferases to study the contribution of the DNMT isotypes to cancer cell methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To explore the role of DNA methyltransferases ( Dnmt ) in acquired drug resistance of neuroblastoma , the present investigation was carried out to study the expression of Dnmtl , Dnmt3a , and Dnmt3b in drug resistant murine neuroblastoma cells , in an in vitro model system . ^^^ The present investigation demonstrates that total Dnmt enzymatic activity was increased two fold ( P < 0 . 001 ) with a 33 % increase in global DNA methylation rate in drug resistant cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
This review describes the role of the DNA methylation mediated repression system ( Dnmt 1 ' s , MeCPs and MBDs and associated chromatin remodelling activities ) in animal development . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Sea urchin DNA ( cytosine 5 ) methyltransferase ( Dnmt 1 ) that is responsible for maintenance of DNA methylation patterns clearly shares similarity with various Dnmt1s identified in vertebrates . ^^^ In this study , we determined the structure of the sea urchin Dnmt 1 gene by screening a genomic library of the sea urchin Paracentrotus lividus with the complementary DNA ( cDNA ) as probe . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To determine if DNMT 1 is involved in the early events of malignant transformation of lymphoid cells , we investigated whether allele specific variation in the gene copy number of DNMT 1 influences susceptibility to the development of malignant lymphoproliferative disease ( LPD ) associated with DNA hypermethylation . ^^^ MATERIALS AND METHODS : DNMT 1 gene copy number was assessed by subjecting DNA from DNMT1A / DNMT1B heterozygous patients suffering from benign LPD or malignant LPD featuring Myf 3 hypermethylation to Southern blotting and densitometric analysis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Human DNA methyltransferase gene DNMT 1 is regulated by the APC pathway . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Impact of Dnmt 1 deficiency , with and without low folate diets , on tumor numbers and DNA methylation in Min mice . ^^^ Dysregulation and instability of DNA methylation and alterations in the levels of the predominant DNA methylating enzyme , DNA ( cytosine 5 ) methyltransferase 1 ( Dnmt 1 ) , have also been linked to tumorigenesis . ^^^ We also show that folate deficiency with or without reductions in Dnmt 1 did not affect overall genomic DNA methylation or the methylation levels of two candidate genes , E cadherin or p 53 , in normal or neoplastic intestinal tissue . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In the mouse , mutations of the oocyte specific isoform of the DNA methyltransferase Dnmt 1 ( Dnmt1o ) and of the methyltransferase like Dnmt3L gene result in specific failures of imprint establishment or maintenance , at multiple loci . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNMT 1 is a component of a multiprotein DNA replication complex . ^^^ In the present study , we show that the predominant DNA methyltransferase species in somatic cells , DNMT 1 , is a component of a multiprotein DNA replication complex termed the DNA synthesome that fully supports semi conservative DNA replication in a cell free system . ^^^ DNMT 1 protein and activity were found to co purify with the human DNA synthesome through a series of subcellular fractionation and chromatography steps , resulting in an enrichment of methyltransferase specific activity from two human cell lines . ^^^ DNA methyltransferase activity co eluted with in vitro replication activity and DNA polymerase alpha activity on sucrose density gradients suggesting that DNMT 1 is a tightly bound , core component of the replication complex . ^^^ The synthesome associated pool of DNA methyltransferase exhibited both maintenance and de novo methyltransferase activity and the ratio of the two was similar to that observed in whole cell lysates and for recombinant DNMT 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We show that knockdown of DNMT 1 ( DNA methyltransferase 1 ) by an antisense oligonucleotide triggers an intra S phase arrest of DNA replication that is not observed with control oligonucleotide . ^^^ The intra S phase arrest of DNA replication is proposed to protect the genome from extensive DNA demethylation that could come about by replication in the absence of DNMT 1 . ^^^ This protective mechanism is not induced by 5 aza 2 ' deoxycytidine , a nucleoside analog that inhibits DNA methylation by trapping DNMT 1 in the progressing replication fork , but does not reduce de novo synthesis of DNMT 1 . ^^^ Our data therefore suggest that the intra S phase arrest is triggered by a reduction in DNMT 1 and not by demethylation of DNA . ^^^ DNMT 1 knockdown also leads to an induction of a set of genes that are implicated in genotoxic stress response such as NF kappaB , JunB , ATF 3 , and GADD45beta ( growth arrest DNA damage 45beta gene ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In agreement with this finding , the expression levels of the prototypic DNA methyltransferase DNMT 1 were elevated in the hTERT positive cells . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Notably , the activity of depsipeptide was enhanced by 5 aza 2 ' deoxycytidine , a DNA methyltransferase inhibitor ( DNMT ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Methylation of these sequences depends on adequate expression of DNA methyltransferase 1 ( DNMT 1 ) during DNA replication . ^^^ In all tumor cell lines , DNMT 1 mRNA as well as protein was decreased relative to the DNA replication factor PCNA , and DNA hypomethylation was present . ^^^ Diminished DNMT 1 : PCNA mRNA ratios were also found in 28 / 45 TCC tissues but did not correlate with the extent of DNA hypomethylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Hypermethylation of cell cycle regulators and increased DNA methyltransferase 1 ( Dnmt 1 ) mRNA level have been reported in hepatocarcinogenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We find that cloned preimplantation mouse embryos aberrantly express the somatic form of the Dnmt 1 DNA ( cytosine 5 ) methyltransferase , the expression of which is normally prevented by a posttranscriptional mechanism . ^^^ Furthermore , aberrant Dnmt 1 localization and expression may contribute to the defects in DNA methylation and the developmental abnormalities seen in cloned mammals . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Biochemical fractionation reveals association of DNA methyltransferase ( Dnmt ) 3b with Dnmt 1 and that of Dnmt 3a with a histone H 3 methyltransferase and Hdac 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Arabidopsis MET 1 ( METHYLTRANSFERASE 1 , ortholog of mammalian DNA methyltransferase Dnmt 1 ) is necessary for maintaining genomic cytosine methylation at 5 ' CG 3 ' sites . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
OBJECTIVE : To determine whether hydralazine might decrease DNA methyltransferase ( DNMT ) expression and induce autoimmunity by inhibiting extracellular signal regulated kinase ( ERK ) pathway signaling . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mutation of the DNA methyltransferase ( DNMT ) 1 gene in human colorectal cancers . ^^^ DNA methyltransferase ( DNMT ) 1 is a major enzyme that determines genomic methylation patterns . ^^^ These data suggest that mutational inactivation of the DNMT 1 gene that potentially causes a genome wide alteration of DNA methylation status may be a rare event during human carcinogenesis . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To determine the role of DNA methylation in replication timing of imprinted loci , we analyzed replication timing in Dnmt 1 and Dnmt3L deficient embryonic stem ( ES ) cells , which lack differential DNA methylation and imprinted gene expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Endogenous assays of DNA methyltransferases : Evidence for differential activities of DNMT 1 , DNMT 2 , and DNMT 3 in mammalian cells in vivo . ^^^ We used an antibody based method to identify specific endogenous DNMTs ( DNMT 1 , DNMT1b , DNMT 2 , DNMT3a , and DNMT3b ) that stably and selectively bind to genomic DNA containing 5 aza 2 ' deoxycytidine ( aza dC ) in vivo . ^^^ Selective binding to aza dC containing DNA suggests that the engaged DNMT is catalytically active in the cell . ^^^ DNMT 1 and 3b displayed the greatest in vivo binding avidity for aza dC containing genomic DNA in these cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In mammals , the DNA methyltransferase 1 ( Dnmt 1 ) faithfully copies the pattern of cytosine methylation at CpG sites to the newly synthesized strand , and this is essential for epigenetic inheritance . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
MG 98 , a phosphorothioate antisense oligodeoxynucleotide that is a specific inhibitor of mRNA for human DNA methyltransferase 1 ( DNMT 1 ) , was evaluated in a phase 1 study . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We find that SUV39H1 also binds to Dnmt 1 and , consistent with these interactions , SUV39H1 can purify DNA methyltransferase activity from nuclear extracts . ^^^ In addition , we show that HP1beta , a SUV39H1 interacting partner , binds directly to Dnmt 1 and Dnmt3a and that native HP1beta associates with DNA methyltransferase activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Increased protein expression of DNA methyltransferase ( DNMT ) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas . ^^^ DNA methyltransferase ( DNMT ) 1 is a major enzyme involved in establishing genomic methylation patterns . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Second , dietary factors may modify the utilization of methyl groups by processes including shifts in DNA methyltransferase ( Dnmt ) activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The present study was designed to investigate the potential relationship between CDKN2A ( p 16 ) gene hypermethylation , which has reported to be frequently observed in oral squamous cell carcinomas ( OSCCs ) , and expression of human DNA methyltransferases ( DNMTs : DNMT 1 , DNMT3A and DNMT3B ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation plays a crucial role in embryogenesis , and Dnmt 1 is known to be a key enzyme in the maintenance of DNA methylation . ^^^ Monoclonal antibody neither inhibited DNA methylation activity of Dnmt 1 in vitro nor affected its stability in embryos . ^^^ The results suggest that the inhibition of cell division by monoclonal antibodies was due neither to the direct inhibition of DNA methylation activity of Dnmt 1 nor to aberrant transcription before the midblastula transition . ^^^ Dnmt 1 may have an important function other than DNA methylation activity for early embryogenesis in Xenopus laevis . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression , and was associated with a higher expression of DNA methyltransferase DNMT 3A . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We concluded that loss of E cadherin expression was in part correlated with DNA methylation and DNMT 1 expression in cervical cancer . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The potential anticancer activities of histone deacetylase ( HDAC ) inhibitors and DNA methyltransferase ( DNMT ) inhibitors have been extensively studied in recent years . ^^^ DNMT inhibitors , such as 5 aza cytidine ( 5 aza CR ) and 5 aza 2 ' deoxycytidine ( 5 aza CdR ) are also widely studied because DNA hypomethylation induces the re activation of tumor suppressor genes that are silenced by methylation mediated mechanisms . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
BACKGROUND : In mammals , epigenetic information is established and maintained via the postreplicative methylation of cytosine residues by the DNA methyltransferases Dnmt 1 , Dnmt3a and Dnmt3b . ^^^ Contrary to Dnmt3a or Dnmt3b , the isolated C terminal region of Dnmt 1 is catalytically inactive , despite the presence of the sequence motifs typical of active DNA methyltransferases . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
PURPOSE : MG 98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase 1 ( DNMT 1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Transcription of mouse DNA methyltransferase 1 ( Dnmt 1 ) is regulated by both E2F Rb HDAC dependent and independent pathways . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The DNA methyltransferase 1 ( DNMT 1 ) protein represents a major DNA methyltransferase activity in human cells and is therefore a prominent target for experimental cancer therapies . ^^^ Based on the strong conservation of catalytic DNA methyltransferase domains we have used a homology modeling approach to determine the three dimensional structure of the DNMT 1 catalytic domain . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Moreover , CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases , DNMT 1 and DNMT3b , as their genetic inactivation restored CHFR expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA hypomethylation and imbalanced expression of DNA methyltransferases ( DNMT 1 , 3A , and 3B ) in human uterine leiomyoma . ^^^ MRNA level of DNA methyltransferases ( DNMT 1 , 3A , and 3B ) was assessed by quantitative real time PCR . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Treatment of spontaneously immortal Li Fraumeni fibroblasts with 5 aza 2 ' deoxycytidine ( 5AZA dC ) , an inhibitor of DNA methyltransferase ( DNMT ) , induces a senescence like state . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The recent characterization of the DNA methyltransferases Dnmt and their protein partners have helped to understand the molecular basis underlying methylation mediated gene silencing and its involvement in cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this paper , we investigated the impact of methylation levels in the cell on mitoxantrone induced cytotoxicity using the colon cancer cell line HCT 116 and its derived DNA methyltransferase ( DNMT ) 1 and DNMT 3a knockout ( DKO 8 ) cell line . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We show that the controlled knockdown of DNA methyltransferase 1 ( DNMT 1 ) in human cancer resulted in growth arrest . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In contrast , overexpression of Dnmt 1 and Dnmt3b3 failed to restore DNA methylation patterns due to their inability to catalyze de novo methylation in vivo . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The Dnmt 1 is one of the DNA methyltransferases that catalyzed DNA methylation on CpG dinucleotides . ^^^ The Dnmt 1 is constitutively expressed and is required for the maintenance of global methylation after DNA replication . ^^^ In this study , we investigated the effects of histone deacetylase ( HDAC ) inhibitor and DNA demethylation agent on promoter activity of mouse Dnmt 1 gene in somatic cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we report a functional search for hypermethylated CpG islands using the colorectal cancer cell line HCT 116 , in which two major DNA methyltransferases , DNMT 1 and DNMT3b , have been genetically disrupted ( DKO cells ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Work presented here raises new and significant hypotheses that must be considered both regarding the cadre of DNA methyltranferases that direct epigenetic programming during normal development and regarding the implication of abnormal DNMT expression in cloned embryos . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The Dnmt 1 gene is constitutively expressed and is required for the maintenance of global methylation after DNA replication . ^^^ We investigated here the effects of histone deacetylase ( HDAC ) inhibitor and DNA demetylation agent on promoter activity of mouse Dnmt 1 gene in somatic cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A loss of imprinting model based on stochastic errors in the nucleocytoplasmic trafficking of the DNA methyltransferase DNMT 1 , or a paternally expressed function that opposes maintenance methylation of maternally repressed growth enhancing genes , is proposed to explain the perplexing genetics of BWS in monozygotic twins . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The preference of murine DNA ( cytosine 5 ) methyltransferase ( Dnmt 1 ) for single stranded DNA substrates is increased up to 50 fold by the presence of a proximal 5 methyl cytosine ( 5 ( me ) C ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To address this question , we used Restriction Landmark Genome Scanning to analyze the susceptibility of 1 , 749 unselected CpG islands to de novo methylation driven by overexpression of DNA cytosine 5 methyltransferase 1 ( DNMT 1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Since the discovery of the DNA methyltransferase ( Dnmt ) inhibitory activity of two azanucleosides ( 5 azacytidine , 5 aza 2 ' deoxycytidine / decitabine ) even at doses with minimal nonhematologic toxicity , both have been clinically studied in several myeloid neoplasias , particularly in elderly patients unable to tolerate aggressive treatment . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
PURPOSE : Three genes , namely DNA methyltransferase ( DNMT ) 1 , DNMT3A , and DNMT3B , coding for DNMTs that affect promoter methylation status are thought to play an important role in the development of cancers . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Double RNA interference of DNMT3b and DNMT 1 enhances DNA demethylation and gene reactivation . ^^^ In this study , we used specific siRNAs as a tool to probe the relationship between two DNA methyltransferase genes , DNMT3b and DNMT 1 , in the maintenance of DNA methylation patterns in the genome . ^^^ The DNMT 1 siRNA treatment led to a partial removal of DNA methylation from three inactive promoter CpG islands , TWIST , RASSF1A , and HIN 1 , and restored the expression of these genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA ( cytosine 5 ) methyltransferase ( DNMT ) catalyzes the transfer of a methyl group from S adenosyl L methionine ( SAM ) to C 5 of cytosine within CpG dinucleotide sequences in the genomic DNA of higher eukaryotes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The presence of DNMT 1 in DNA replication foci raises the issue of whether this enzyme needs to gain access to nascent DNA before its packaging into nucleosomes , which occurs very rapidly behind the replication fork . ^^^ Using nucleosomes positioned along the 5 S rRNA gene , we find that DNMT 1 is able to methylate a number of CpG sites even when the DNA major groove is oriented toward the histone surface . ^^^ However , we also find that the ability of DNMT 1 to methylate nucleosomal sites is highly dependent on the nature of the DNA substrate . ^^^ These results argue that although DNMT 1 is intrinsically capable of methylating some DNA sequences even after their packaging into nucleosomes , this is not the case for at least a fraction of DNA sequences whose function is regulated by DNA methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Recent studies have shown that the methyltransferases DNMT 1 and DNMT3b cooperatively maintain DNA methylation and gene silencing in human cancer cells . ^^^ Disruption of the human DNMT3b only slightly reduces the overall global DNA methylation ; however , demethylation was markedly potentiated when both DNMT 1 and DNMT3b were simultaneously deleted . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To determine the effects of paternal 5 aza 2 ' deoxycytidine treatment on spermatogenesis and progeny outcome in the mouse and whether effects are modulated by decreased levels of the predominant DNA methyltransferase , DNMT 1 , adult Dnmt 1 ( + / + ) and Dnmt 1 deficient ( Dnmt 1 ( c / + ) ) male mice were treated with 5 aza 2 ' deoxycytidine for 7 weeks , which resulted in dose dependent decreases in testicular weight , an increase in histological abnormalities , and a decline in sperm counts , with no apparent effect on androgen status . ^^^ Altered DNA methylation or DNMT 1 activity may explain such adverse effects , because treatment resulted in dose dependent decreases in the global methylation of sperm DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Deletion of p53in HCT 116 human colon carcinoma cells and primary mouse astrocytes resulted in a 6 fold increase of DNA cytosine methyltransferase 1 ( Dnmt 1 ) mRNA and protein , suggesting relief of p 53 mediated Dnmt1repression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Type 2 polarization blocks Dnmt 1 recruitment , enhances histone H 3 Lys4 methylation ( indicative of accessible chromatin ) and initiates DNA demethylation of the locus . ^^^ Dnmt 1 / CD 4 and CD 8 T cells derepress IL 4 expression considerably , demethylate DNA and increase H 3 Lys4 methylation without affecting GATA 3 expression , demonstrating that Dnmt 1 and DNA methylation are essential for proper Il 4 regulation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Disruption of one allele for the cytosine DNA methyltransferase 1 ( DNMT 1 ) gene in mice with a germ line mutation in a tumor suppressor gene was shown previously to reduce tumor formation in juvenile animals . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
This study addresses the hypothesis that specific inhibition of the maintenance DNA methyltransferase , DNMT 1 , by antisense oligonucleotides ( DNMT 1 ASO ) is sufficient to re express the ER gene in ER negative human breast cancer cell lines . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To explore this phenomenon , we generated mice carrying a hypomorphic DNA methyltransferase 1 ( Dnmt 1 ) allele , which reduces Dnmt 1 expression to 10 % of wild type levels and results in substantial genome wide hypomethylation in all tissues . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Assignment of DNA cytosine 5 methyltransferase 1 ( DNMT 1 ) gene to porcine chromosome 2q21 > q 22 by somatic cell and radiation hybrid panel mapping . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The expression of DNA methyltransferase DNMT 1 , 3A and 3B in acute leukemia and myelodysplastic syndrome ] . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5 cytosine DNA methyltransferase ( DNMT ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We elucidated the significance of aberrant protein expression of DNA methyltransferase ( DNMT ) 1 , a major enzyme involved in the determination of genomic methylation patterns , during human urothelial carcinogenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mammalian DNA methylation patterns are established and maintained by co operative interactions among the Dnmt proteins Dnmt 1 , Dnmt3a and Dnmt3b . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we show that the p33ING1 Sin 3 HDAC complex as well as DNA methyltransferase 1 ( DNMT 1 ) and DNMT 1 associated protein 1 ( DMAP 1 ) are components of a pathway required for maintaining proper histone modification and heterochromatin protein 1 binding at the pericentric heterochromatin . p33ING1 and DMAP 1 interact physically and co localize to heterochromatin in the late S phase , and both are required for heterochromatin protein 1 binding to heterochromatin . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The drug caused a complete depletion of extractable DNA methyltransferase 1 ( DNMT 1 ) and partial depletion of DNMT3a and DNMT3b3 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
METHODS : Two gastric cancer cell lines ( MKN 45 and HGC 27 ) were treated with DNA methyltransferase ( DNMT ) inhibitor , 5 aza 2 ' deoxycytidine ( 5 aza dC ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
RESULTS : Our results indicated that treatment with 5 aza deoxycytidine ( 5 aza C ) , a demethylating agent , increased the transcription of messenger RNA ( mRNA ) for HERV clone 4 1 and decreased mRNA for DNA methyltransferase 1 ( DNMT 1 ; methylation regulating enzyme ) in peripheral blood mononuclear cells ( PBMC ) from normal individuals . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Increased DNA methyltransferase 1 ( DNMT 1 ) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers . ^^^ We evaluated the significance of aberrant DNA methyltransferase 1 ( DNMT 1 ) protein expression during gastric carcinogenesis . ^^^ Reduced E cadherin expression correlated significantly with poorer tumor differentiation ( P = 0 . 002 ) , DNA hypermethylation of the E cadherin gene ( P < 0 . 001 ) and DNMT 1 overexpression ( P = 0 . 014 ) . ^^^ Furthermore , DNMT 1 may play a significant role in the development of poorly differentiated gastric cancers by inducing frequent DNA hypermethylation of multiple CpG islands . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It has been suggested that the high levels of DNA methyltransferase 1 ( Dnmt 1 ) present during cleavage could be important for keeping IAPs methylated . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Several alternatively spliced variants of DNA methyltransferase ( DNMT ) 3b have been described . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) associated protein ( DMAP 1 ) was identified and demonstrated to interact with Daxx . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Increased DNA ( cytosine 5 ) methyltransferse ( Dnmt 1 ) activity is involved in the mechanism of transformation by both oncogenes , suggesting that inappropriate epigenetic transcription regulation may be a common route of oncogenesis , and that cell transformation may model aspects of the epigenetic deregulation that often occurs in tumors . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
METHODS : Two colon cancer cell lines ( SW 1116 and Colo 320 ) were treated with the DNA methyltransferase ( DNMT ) inhibitor , 5 aza 2 ' deoxycytidine ( 5 aza dC ) and / or the histone deacetylase ( HDAC ) inhibitor , trichostatin A ( TSA ) or sodium butyrate ( NaBu ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We compared the temporal expression patterns of the DNA methyltransferases , DNMT 1 , DNMT3a , DNMT3b , and DNMT3l in the male and female germ lines . ^^^ In the male , DNMT 1 is unlikely to play a role in the prenatal acquisition of germ line methylation patterns since it is down regulated in gonocytes between 14 . 5 and 18 . 5 days of gestation and is absent at the time of initiation of DNA methylation . ^^^ DNMT3l is the predominant DNMT 3 enzyme expressed at high levels in the postnatal female germ line at the time of acquisition of DNA methylation patterns . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Consistent with this hypothesis , we report that DNA methyltransferase 1 ( Dnmt 1 ) knockout ES cells show a 2 fold increase in gene targeting frequency . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) catalyzes the post replication methylation of DNA and is responsible for maintaining the DNA methylation pattern during cell division . ^^^ We have previously shown that DNMT 1 knock down by either antisense oligonucleotides directed at DNMT 1 or expressed antisense activates a number of genes involved in stress response and cell cycle arrest by a DNA methylation independent mechanism . ^^^ In this report we demonstrate that antisense knock down of DNMT 1 in human lung carcinoma A 549 and embryonal kidney HEK 293 cells induces gene expression by a mechanism that does not involve either of the known epigenomic mechanisms , DNA methylation , histone acetylation , or histone methylation . ^^^ Our data suggest a fundamentally different and surprising role for DNMT 1 regulation of CG rich genes by a mechanism independent of DNA methylation and histone acetylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNMT3L enhanced the DNA methylation activity of Dnmt3a and Dnmt3b about 1 . 5 3 fold in a dose dependent manner but did not enhance the DNA methylation activity of Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The non random pattern of genome wide DNA methylation in mammalian cells is established and maintained by DNA methyltransferases DNMT 1 , 3A , and 3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) is required to maintain DNA methylation patterns in mammalian cells , and is thought to be the predominant maintenance methyltransferase gene . ^^^ Recent studies indicate that inhibiting DNMT 1 protein expression may be a useful approach for understanding the role of DNA methylation in tumorigenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The DNA methylation is carried out by DNA methyltransferases ( DNMT ) and it serves as an epigenetic method of gene expression modulation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Proper patterns of genome wide DNA methylation , mediated by DNA methyltransferases DNMT 1 , 3A and 3B , are essential for embryonic development and genomic stability in mammalian cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The role of the primary mammalian DNA methyltransferase , DNMT 1 , in maintaining CpG island methylation in human colon cancer cells has recently been questioned . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The correlation of PR methylation and expression together with DNA methyltransferase ( DNMT 1 ) was further studied . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation is mediated by DNA methyltransferases ( DNMTs ) , of which three active forms have been identified : DNMT 1 , DNM3A and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) plays an essential role in murine development and is thought to be the enzyme primarily responsible for maintenance of the global methylation status of genomic DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In mammals , DNA methylation is mediated by at least four DNA methyltransferase ( Dnmt ) enzymes , including Dnmt 1 , Dnmt 2 , Dnmt3a , and Dnmt3b . ^^^ To understand fully how DNA methylation is involved in gene regulation , knowledge of Dnmt mRNA transcript levels is required , both as a surrogate measure of Dnmt protein levels and also to facilitate an understanding of the regulation of expression of the corresponding genes . ^^^ This technique is both sensitive and specific and allows for the rapid assessment of Dnmt mRNA transcript levels as well transcripts for other genes that may be involved in DNA methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The role of DNA methyltransferase 1 , DNMT 1 , in human cancer cells has recently been contested . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA ( cytosine 5 ) methyltransferase 1 ( DNMT 1 ) plays an important role in the maintenance of DNA methylation patterns via complicated networks including signaling pathways and transcriptional factors , relating to cell differentiation or carcinogenesis . ^^^ In conclusion , the inhibition of DNA methylation by DNMT 1 by an antisense oligodeoxynucleotide influences cell morphology and adhesion , as well as cell growth in gastric cancer cells in vitro . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To elucidate how DNA methyltransferases ( Dnmts ) participate in methylation of the genomic components , we investigated the genome wide DNA methylation pattern of the T DMRs with Dnmt 1 , Dnmt3a , and / or Dnmt3b deficient ES cells by restriction landmark genomic scanning ( RLGS ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
OBJECTIVE : To analyze the effect of eukaryotic plasmids containing sense or antisense DNA methyltransferase ( Dnmt 1 ) genes on the methylation status and transcription level of DNA mismatch repair ( MMR ) genes and microsatellite instability ( MSI ) in human colon cancer cell line . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Effects of chromatin structure on the enzymatic and DNA binding functions of DNA methyltransferases DNMT 1 and Dnmt3a in vitro . ^^^ It remains unclear , however , exactly how chromatin and epigenetic chromatin modifications affect the biological properties of the DNA methyltransferases ( DNMT 1 , DNMT3A , and DNMT3B ) . ^^^ Using a highly purified system and the 5S rDNA gene as free DNA or assembled into a mononucleosome , we have compared the effects of chromatin structure on DNMT 1 and Dnmt3a . ^^^ DNMT 1 and Dnmt3a bound to DNA and mononucleosomal substrates in gel shift experiments with approximately equal affinity and in a cooperative manner . ^^^ These findings raise interesting implications about the interactions of mammalian DNA methyltransferases with chromatin and provide the first evidence that a chromatin remodeling enzyme can alter the biological properties of a DNMT . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In addition , zebularine preferentially depleted DNA methyltransferase 1 ( DNMT 1 ) and induced expression of cancer related antigen genes in cancer cells relative to normal fibroblasts . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A mutation may be present in the gene but undetected , present in other DNA methyltransferases ( DNMT ) genes or in a DNMT associated protein gene . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The Dnmt 1 DNA ( cytosine C 5 ) methyltransferase methylates DNA processively with high preference for hemimethylated target sites . ^^^ In the cell , Dnmt 1 is the major enzyme in maintenance of the pattern of DNA methylation after DNA replication . ^^^ To elucidate the potential mechanism of this process , we investigate the processivity of DNA methylation and accuracy of copying an existing pattern of methylation in this study using purified Dnmt 1 and hemimethylated substrate DNA . ^^^ Completely unmodified DNA is methylated even more slowly due to an allosteric activation of Dnmt 1 by methylcytosine containing DNA . ^^^ Interestingly , Dnmt 1 is not able to methylate hemimethylated CG sites on different strands of the DNA in a processive manner , indicating that Dnmt 1 keeps its orientation with respect to the DNA while methylating the CG sites on one strand of the DNA . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Herein , we show that the enzymatic activity of DNMT 1 , the primary DNA methyltransferase in mammalian cells , is inhibited by DNA intercalators , such as doxorubicin , in an in vitro assay . ^^^ Enzymatic analyses indicate that doxorubicin inhibits the catalytic activity of DNMT 1 via DNA intercalation . ^^^ We also found that apoptosis was induced in DNMT 1 ( + / + ) HCT 116 cells by only a limited range of doxorubicin dose , meaning that apoptotic cell death is `` conditional ' ' with respect to the concentration of the DNA intercalating drug . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To investigate the effect of 5 aza 2 ' deoxycytidine ( 5 Aza CdR ) on cell of high risk patients with myelodysplastic syndrome ( MDS ) in vitro , the growth inhibition of MUTZ 1 cell induced by 5 Aza CdR was detected by MTT method ; apoptosis was detected by morphological observation and translocation of phosphatidylserine ( PS ) was examined by flow cytometry assay ; the expressions of P15INK4B , DNA methyltransferases ( DNMT ) ( 1 ) , DNMT ( 3A ) and DNMT ( 3B ) gene on mRNA level were detected by RT PCR ; methylation of p15INK4B gene in MUTZ 1 cells was detected by PCR using methylation specific primer ( MSP ) . ^^^ Furthermore , 5 Aza CdR could significantly down regulate the expressions of DNA methyltransferase genes DNMT ( 3A ) at mRNA level in a dose dependent manner . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In the present study , the association between a novel functional C / T polymorphism in the core promoter of cytosine DNA methyltransferase ( DNMT ) 3B6 and overall survival of HNSCC patients was investigated . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Association analyses of DNA methyltransferase 1 ( DNMT 1 ) polymorphisms with systemic lupus erythematosus . ^^^ DNA methyltransferase 1 ( DNMT 1 ) is a major enzyme that determines genomic methylation patterns and both maintains methyltransferase and exhibits de novo DNA methylation activity in vivo . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase Dnmt 1 and mismatch repair . ^^^ We have examined the relationship between DNA mismatch repair and deficiency of DNA methylation in a mouse embryonic cell line , Dnmt 1 / ES , with homologous deletion of the gene coding for the maintenance DNA methyltransferase Dnmt 1 . ^^^ The data suggest that Dnmt 1 enzyme plays an integrating role in DNA replication and / or repair . ^^^ The implication that Dnmt 1 enzyme and / or cytosine methylation may participate in the strand discrimination of mismatch repair during eukaryotic DNA replication is discussed . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Peptide p 1028 ( GLIEKNIEL ) , derived from DNA methyltransferase 1 ( DNMT 1 ) , which is overexpressed in various human tumors , showed the highest affinity to HLA A 2 and was relatively abundant in the sMHC / peptide complexes of all transfected breast , ovarian and prostate cancer cell lines . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this study , we show that in the absence of the maintenance DNA methyltransferase Dnmt 1 , silencing of IL 4 , IL 5 , IL 13 , and IL 10 in CD 8 T cells was abolished , and expression of these Th 2 cytokines increased as much as 1000 fold compared with that of control CD 8 T cells . ^^^ These results indicate that Dnmt 1 and DNA methylation are necessary to prevent cell autonomous Th 2 cytokine expression in CD 8 T cells but are not essential for maintaining proper T cell subset specific expression of Th 1 or CTL effectors . ^^^ We also found that the expression of Th 2 cytokines by Dnmt 1 ( / ) T cells was appropriately up regulated in Th 2 conditions and down regulated in Th 1 conditions , indicating that transcription factors and DNA methylation are complementary and nonredundant mechanisms by which the Th 2 effector program is regulated . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It has been reported that DNA methyltransferase 1 deficient ( Dnmt 1 / ) embryonic stem ( ES ) cells are hypomethylated ( 20 % CpG methylation ) and die through apoptosis when induced to differentiate . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
One of the most perplexing questions regarding epigenetic modifications and leukemogenesis is the relationship with DNA methyltransferases ( DNMT ' s ) . ^^^ The primary function of the DNMT enzymes is to methylate genomic DNA , whereas the methyl CpG binding domain proteins ( MBD ) interpret this methylation signal and regulate gene expression and chromatin behavior . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The methylation and resultant silencing of CIITA PIV depended on the activities of two DNA methyltransferases , DNMT 1 and DNMT3B , and their genetic inactivation restored CIITA PIV expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Treatment of non expressing cells with the DNA methyltransferase ( DNMT ) inhibitor 5 aza 2 ' deoxycytidine reduces cytosine methylation of the Rac 2 gene locus and is sufficient to induce Rac 2 gene expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We tested the hypothesis that the effects on gene expression of altered DNA methylation by 5 aza 2 ' deoxycytidine ( 5 aza CdR ) and genetic ( DNMT knockout ) manipulation of DNA are similar , and distinct from Trichostatin A ( TSA ) induced chromatin decondensation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Overexpression of the major DNA methyltransferase Dnmt 1 is cytotoxic and has been hypothesized to result in aberrant hypermethylation of genes required for cell survival . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Processive methylation of hemimethylated CpG sites by mouse Dnmt 1 DNA methyltransferase . ^^^ DNA methyltransferase Dnmt 1 ensures clonal transmission of lineage specific DNA methylation patterns in a mammalian genome during replication . ^^^ To understand the underlying mechanism of its maintenance function , we purified recombinant forms of full length Dnmt 1 , a truncated form of Dnmt 1 ( 291 1620 ) lacking the binding sites for PCNA and DNA and examined their processivity using a series of long unmethylated and hemimethylated DNA substrates . ^^^ Direct analysis of methylation patterns using bisulfite sequencing and hairpin PCR techniques demonstrated that full length Dnmt 1 methylates hemimethylated DNA with high processivity and a fidelity of over 95 % , but unmethylated DNA with much less processivity . ^^^ Remarkably , our analyses also revealed that Dnmt 1 methylates hemimethylated CpG sites on one strand of double stranded DNA during a single processive run . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have developed a model system to analyze the effects of DNA methyltransferase 1 ( Dnmt 1 ) deficiency on DNA mismatch repair ( MMR ) in mouse embryonic stem ( ES ) cells . ^^^ Interestingly , the region flanking the mononucleotide repeat was unmethylated regardless of Dnmt 1 status , suggesting that it is not the local levels of DNA methylation that direct the increase in microsatellite instability ( MSI ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we review our current understanding of the molecular enzymology of the mammalian DNA methyltransferases Dnmt 1 , Dnmt3a , Dnmt3b and Dnmt 2 and the roles of the enzymes in the above mentioned biological processes . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Recent clinical studies have shown that the DNA methyltransferase ( DNMT ) inhibitor decitabine effectively increased HbF in hydroxyurea refractory patients . ^^^ The rational use of DNMT inhibitors as therapeutic agents to reactivate HbF expression in patients with sickle cell disease is based on nearly 25 years of experimental evidence , reviewed in this article , that supports a fundamental role of DNA methylation in the silencing of gamma globin gene expression in adults . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Decreased HbF production is associated with DNA methylation ( by DNA methyltransferase [ DNMT ] ) at the gamma globin ( HbF ) gene promoter . ^^^ The cytosine analogs 5 azacytidine and 5 aza 2 ' deoxycytidine ( decitabine ) hypomethylate DNA by inhibiting DNMT . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA ( cytosine 5 ) methyltransferase ( Dnmt ) , a methylating enzyme of cytosine residues on CpG dinucleotides , plays an important role in 10 chromosome inactivation , genomic imprinting , and gene expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A deeper knowledge about their apotosis inducing mechanisms and their interaction with DNA methyltransferases ( DNMTs ) DNMT 1 , DNMT3a , and DNMT3b might allow the design of more effective drugs with lower cytotoxicity . 5 aza cytidine ( 5 aza CR ) , a potent inhibitor of DNMT 1 , is known to induce demethylation and reactivation of silenced genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The major DNA methyltransferase , Dnmt 1 , associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand . ^^^ Using time lapse microscopy of mammalian cells expressing green fluorescent protein tagged Dnmt 1 and DsRed tagged DNA Ligase 1 as a cell cycle progression marker , we have found that Dnmt 1 associates with chromatin during G 2 and M . ^^^ Moreover , photobleaching analyses showed that Dnmt 1 is continuously loaded onto chromatin throughout G 2 and M , indicating a replication independent role of Dnmt 1 that could represent a novel and separate pathway to maintain DNA methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We tested the hypothesis that up regulation of DNA methyltransferase 1 ( DNMT 1 ) will lead to methylation and silencing of uPA and inhibition of the invasiveness of metastatic breast cancer cells . ^^^ We then examined the levels of DNMT 1 and methylated DNA binding protein 2 ( MBD 2 ) expressions in these cells to determine whether this reduction in uPA expression is associated with changes in the DNA methylation machinery . ^^^ These results therefore imply that the RAS DNMT 1 DNA methylation pathway which promotes oncogenic growth in many cancers can exert an opposite effect on the invasive capacity of the highly invasive MDA MB 231 cells , thus illustrating the divergence of growth and metastasis promoting pathways in cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Stage by stage change in DNA methylation status of Dnmt 1 locus during mouse early development . ^^^ Three isoforms of Dnmt 1 ( DNA methyltransferase 1 ) transcripts , Dnmt1s , Dnmt1o , and Dnmt1p , are produced by alternative usage of multiple first exons . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this issue of Oncogene , Reale et al . report the formation of a particularly sophisticated complex of two important regulatory enzymes , DNMT 1 ( DNA methyltransferase 1 ) and PARP 1 ( poly ( ADP ribose ) polymerase 1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Binding of poly ADP ribose on DNMT 1 inhibits DNA methyltransferase activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA ( cytosine 5 ) methyltransferase ( DNMT ) 1 participates in transcriptional repression of genes by methylation dependent and independent mechanisms . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Up regulation of DNA methyltransferases DNMT 1 , 3A , and 3B in myelodysplastic syndrome . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
CG sites are maintained by a plant homolog of mammalian Dnmt 1 acting on hemi methylated DNA after replication . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Approximately 83 % of the neurons are GABAergic based on GAD immunoreactivity , and these neurons coexpress high levels of reelin and DNA methyltransferase ( Dnmt ) 1 immunoreactivity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The acute promyelocytic leukemia ( PML ) retinoic acid receptor alpha ( RARalpha ) fusion product recruits histone deacetylase ( HDAC ) and DNA methyltransferase ( DNMT ) activities on retinoic acid ( RA ) target promoters causing their silencing and differentiation block . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Based on the different nuclear distribution of DNA Ligase 1 and Dnmt 1 in G 2 and G 1 , we demonstrate that the combination of both proteins allows the direct discrimination of all cell cycle phases using either immunostainings or fusions with fluorescent proteins . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The ectopic expression of DNA methyltransferase 1 ( DNMT 1 ) can transforms mammalian cells , and the inhibition of DNMT 1 activity reverses that phenotypic transformation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
OBJECTIVE : To examine the DNA methyltransferase ( DNMT ) mRNA and protein levels in endometrioid and serous cancers and to study the relationship between DNA methyltransferase expression and endometrial cancer development . ^^^ Real time PCR and Western blot techniques were employed to measure the mRNA and protein levels of the four DNA methyltransferases , DNMT 1 , DNMT 2 , DNMT3A , and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We previously reported that expression of the RUNX1 / MTG8 target gene IL 3 is synergistically restored by the combination of inhibitors of HDACs ( i . e . , depsipeptide ) and DNA methyltransferases ( DNMT ; i . e . , decitabine ) in RUNX1 / MTG8 positive Kasumi 1 cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It has been accepted that the mechanism of toxicity is due to the covalent binding between the DNA methyltransferase ( Dnmt ) and 5 aza dC substituted DNA . ^^^ Further , the ability to form Dnmt DNA adducts was similar in Dnmt 1 and Dnmt 3 , and the expression level of Dnmt 3 was not higher than that of Dnmt 1 in ES cells . ^^^ Therefore , Dnmt 3 DNA adducts may be more effective for inducing apoptosis than Dnmt 1 DNA adducts . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Recent studies using hypomorphic DNA methyltransferase 1 ( DNMT 1 ) alleles have suggested that strategies aiming to reduce DNA methylation may increase genomic instability and lymphomagenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase ( DNMT ) 3A and DNMT3B are both active de novo DNA methyltransferases required for development , whereas DNMT3L , which has no demonstrable methyltransferase activity , is required for methylation of imprinted genes in the oocyte . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We report that DNA methyltransferase 1 ( DNMT 1 ) expression is dysregulated in breast cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Our studies led to the following observations . 1 ) Constitutive or conditional deletion of Dnmt3b , but not Dnmt3a , resulted in partial loss of DNA methylation throughout the genome , suggesting that Dnmt3b , in addition to the major maintenance methyltransferase Dnmt 1 , is required for maintaining DNA methylation in MEF cells . 2 ) Dnmt3b deficient MEF cells showed aneuploidy and polyploidy , chromosomal breaks , and fusions . 3 ) Inactivation of Dnmt3b resulted in either premature senescence or spontaneous immortalization of MEF cells . 4 ) The G ( 1 ) to S phase checkpoint was intact in primary and spontaneously immortalized Dnmt3b deficient MEFs because the p 53 protein was inducible by DNA damage . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Increased DNA methyltransferase 1 ( DNMT 1 ) gene expression in human lymphomas by fluorescent in situ hybridization . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
After 12 wk , dietary arsenic affected the number of aberrant crypts ( p < 0 . 02 ) and aberrant crypt foci ( p < 0 . 007 ) in the colon and the amount of global DNA methylation ( p < 0 . 04 ) and activity of DNA methyltransferase ( DNMT ) ( p < 0 . 003 ) in the liver . ^^^ In each case , there were more aberrant crypts and aberrant crypt foci , a relative DNA hypomethylation , and increased activity of DNMT in the rats fed 50 microg As / g compared to those fed 0 . 5 microg As / g . ^^^ The same phenomenon , an increased number of aberrant crypts and aberrant crypt foci , DNA hypomethylation , and increased DNMT tended to hold when comparing rats fed the diet containing no supplemental arsenic compared to rats fed 0 . 5 microg As / g . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Silencing of MLL WT in MLL ( PTD / WT ) blasts was reversed by DNA methyltransferase ( DNMT ) and histone deacetylase ( HDAC ) inhibitors , and MLL WT induction was associated with selective sensitivity to cell death . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It has been observed that decrease of DNA methyltransferase 1 ( DNMT 1 ) activity is associated with low content of the CD 3 zeta ( zeta ) chain in T cell receptor ( TCR ) / CD3 complex of T cells in systemic lupus erythematosus ( SLE ) patients . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
BACKGROUND : Though Dnmt 1 is considered the primary maintenance methyltransferase and Dnmt3a and Dnmt3b are considered de novo methyltransferases in mammals , these three enzymes may work together in maintaining as well as establishing DNA methylation patterns . ^^^ CONCLUSION : The fact that Dnmt3a does not act on single stranded DNA and is not stimulated by pre existing cytosine methylation indicates that the de novo methylation activity of Dnmt3a is quite different from that of Dnmt 1 . ^^^ These findings are consistent with a model in which Dnmt3a initiates methylation on one of the DNA strands of duplex DNA , and these hemimethylated sites then stimulate Dnmt 1 activity for further methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It is well known that the histone deacetylase ( HDAC ) inhibitor trichostatin A ( TSA ) acts synergistically with the DNA methyltransferase ( DNMT ) inhibitor 5 aza 2 ' deoxycytidine ( ADC ) to reactivate DNA methylation silenced genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA hypermethylation on multiple CpG islands associated with increased DNA methyltransferase DNMT 1 protein expression during multistage urothelial carcinogenesis . ^^^ PURPOSE : We elucidated the significance of aberrant DNA methylation on multiple CpG islands and its correlation with DNA methyltransferase DNMT 1 protein expression during urothelial carcinogenesis . ^^^ In all specimens examined concurrent DNA hypermethylation on 3 or more CpG islands significantly correlated with immunohistochemically evaluated DNMT 1 protein over expression ( p = 0 . 0167 ) . ^^^ CONCLUSIONS : DNA hypermethylation on multiple CpG islands in association with DNMT 1 protein over expression may participate in multistage urothelial carcinogenesis even at the precancerous stage and particularly in the development of nodular invasive carcinomas of the bladder . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Support for this possibility is provided by our observation that Ras transformation was associated with up regulation of Dnmt 1 and Dnmt 3 DNA methyltransferase expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The objective was to study , by real time reverse transcriptase polymerase chain reaction ( RT PCR ) , the effects of postnatal exposure to a reconstituted mixture of AhR agonists present in breast milk ( 3 non ortho PCBs , 6 PCDDs , and 7 PCDFs , referred to here in after as AhRM ) on mRNA expression of estrogen receptor ( ERalpha ) , enzymes involved with the metabolism of estrogens [ catechol o methyltransferase ( Comt ) , cytochrome P 450 ( Cyp ) 1A1 , 1B1 and 2B1 ] , and DNA methyltransferase 1 ( Dnmt 1 ) , in brain areas , liver and uterus of immature female rats . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Elevated expression of the maintenance DNA methyltransferase , DNA methyltransferase 1 ( DNMT 1 ) , has been shown in carcinomas of the colon , lung , liver , and prostate . ^^^ Analysis of DNA methyltransferase levels in Rb / murine prostate epithelial cell lines revealed elevated Dnmt 1 levels . ^^^ Genomic DNA sequence analysis identified conserved E2F consensus binding sites in proximity to the transcription initiation points of murine and human Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We demonstrate that malignant T cells express DNA methyltransferase ( DNMT ) 1 and that constantly activated signal transducer and activator of transcription ( STAT ) 3 is capable of binding in vitro to DNA oligonucleotides corresponding to four STAT 3 SIE / GAS binding sites identified in the SHP 1 promoter . ^^^ Treatment with pharmacologic grade DNMT 1 anti sense oligonucleotides and STAT 3 small interfering RNA induces in the malignant T cells DNA demethylation and expression of SHP 1 gene . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Procainamide is a competitive DNA methyltransferase ( Dnmt ) inhibitor , hydralazine inhibits ERK pathway signaling thereby decreasing Dnmt expression , and in lupus T cells decreased ERK pathway signaling causing a similar Dnmt decrease . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
This inhibition of DNA methyltransferase ( DNMT ) is hypothesized to be mechanism based and result from formation of a covalent complex between the enzyme and zebularine substituted DNA . ^^^ The complex metabolism of Zeb and its limited DNA incorporation suggest that these are the reasons why it is less potent than either 5 azacytidine or 5 aza 2 ' deoxycytidine and requires higher doses for equivalent inhibition of DNMT . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To investigate roles for DNMTs during hepatocarcinogenesis , we examined DNMT expression at both the mRNA and protein level in hepatocellular carcinomas ( HCCs ) and paired non neoplastic liver tissues , along with measuring the DNA methylation status of five tumor suppressor genes . ^^^ There was no significant correlation between DNMT mRNA expression and DNA methylation ( P > 0 . 05 ) . ^^^ DNMT immunoreactivity was also not associated with DNA methylation except HIC 1 ( P=0 . 036 ) and p 53 methylation ( P=0 . 009 ) . ^^^ Despite the lack of correlation between DNA methylation status and DNMT expression , the frequency of hypermethylation of tumor suppressor genes remained relatively high in HCCs , suggesting that regional DNA hypermethylation is involved in hepatocarcinogenesis and that there may be other mechanisms for increasing DNA methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we report that among three functional DNA methyltransferases ( DNMT 1 , DNMT3A , and DNMT3B ) , the maintenance methyltransferase , DNMT 1 , was rapidly degraded by the proteasomal pathway upon treatment of cells with these drugs . ^^^ Mutation of cysteine at the catalytic site of Dnmt 1 ( involved in the formation of a covalent intermediate with cytidine in DNA ) to serine ( CS ) did not impede 5 aza CdR induced degradation . ^^^ These results demonstrate a unique mechanism for the selective degradation of DNMT 1 , the maintenance DNA methyltransferase , by well known DNA hypomethylating agents . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
BLASTX searches and phylogenetic analysis suggested that five cDNAs belonged to four classes ( Dnmt 1 , Dnmt 2 , CMT and Dnmt 3 ) of DNA methyltransferase genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Among the genes examined , DNA methyltransferase 1 ( DNMT 1 ) shows a significantly higher ( P < 0 . 05 ) expression level in cultured embryos . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Genes with the highest upregulation throughout the time course included tubulin genes , ezrin , c1qr1 , fos , pcna , mcm 6 , ung , and dnmt 1 , genes that play an essential role in reorganization of the cytoskeleton system , stabilization of DNA , and methylation patterns . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Using a laser microirradiation system to introduce DNA lesions at defined subnuclear sites , we tested whether the major DNA methyltransferase ( Dnmt 1 ) or one of the two de novo methyltransferases ( Dnmt3a , Dnmt3b ) are recruited to sites of DNA repair in vivo . ^^^ Time lapse microscopy of microirradiated mammalian cells expressing GFP tagged Dnmt 1 , Dnmt3a , or Dnmt3b1 together with red fluorescent protein tagged proliferating cell nuclear antigen ( PCNA ) revealed that Dnmt 1 and PCNA accumulate at DNA damage sites as early as 1 min after irradiation in S and non S phase cells , whereas recruitment of Dnmt3a and Dnmt3b was not observed . ^^^ These data point to a direct role of Dnmt 1 in the restoration of epigenetic information during DNA repair . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Several potential acceptors of cycle generated methyl groups , the DNA methyltransferases ( DNMT 1 , DNMT3A , DNMT3B and DNMT3L ) , glycine methyltransferase and the polyamine biosynthetic enzymes , SAM decarboxylase and ornithine decarboxylase , were also expressed . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Overexpression of Dnmt 1 , a mammalian maintenance DNA methyltransferase , was associated with Apaf 1 gene methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
XCI chromatin remodeling genes , such as histone H 3 methylation enzymes ( SUV39H1 and SET 7 ) and DNA methylation enzyme ( DNMT 1 ) , were expressed during all early phases of embryogenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA cytosine C 5 methyltransferase Dnmt 1 : catalysis dependent release of allosteric inhibition . ^^^ We followed the cytosine C ( 5 ) exchange reaction with Dnmt 1 to characterize its preference for different DNA substrates , its allosteric regulation , and to provide a basis for comparison with the bacterial enzymes . ^^^ Changes in these rapid equilibrium steps account for many of the previously described features of Dnmt 1 catalysis and specificity including faster reactions with premethylated DNA versus unmethylated DNA , faster reactions with DNA in which guanine is replaced with inosine [ poly ( dC dG ) vs poly ( dI dC ) ] , and 10 100 fold slower catalytic rates with Dnmt 1 relative to the bacterial enzyme M . ^^^ Dnmt 1 shows a kinetic lag in product formation and allosteric inhibition with unmethylated DNA that is not observed with premethylated DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Seventy two hours withdrawal of GM CSF+FBS followed by 24 h exposure to inhibitors for DNA methyltransferase ( DNMT ) and histone deacetylase ( HDAC ) caused the demethylation of nearly all CpG sites in the p 15 CpG island on every allele sequenced . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this study , we further speculated that the HPV infection may be linked with the expression of DNA methyltransferase ( DNMT ) protein in lung cancer patients and it was observed that an association of p16INK4a promoter hypermethylation with HPV infection existed , but only in female cases ( P < 0 . 0001 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We report here that conditional gene deletion of the maintenance DNA methyltransferase 1 ( Dnmt 1 ) in neural progenitor cells ( NPCs ) results in DNA hypomethylation and precocious astroglial differentiation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( Dnmt 1 ) is a critical maintenance methyltransferase which , during DNA replication , maintains the DNA methylation patterns of the cellular genome , a process that is essential for the survival of proliferating cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Compared with newborns , the adult mouse brain also had lower levels of Dnmt 1 , the enzyme responsible for maintaining DNA methylation state . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
De novo methylation of nucleosomal DNA by the mammalian Dnmt 1 and Dnmt3A DNA methyltransferases . ^^^ We investigated de novo methylation of nucleosomal DNA in vitro and show that the Dnmt3a and Dnmt 1 DNA methyltransferases efficiently methylate nucleosomal DNA without dissociation of the histone octamer from the DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In the present investigation , we studied the modulating effects of several tea catechins and bioflavonoids on DNA methylation catalyzed by prokaryotic SssI DNA methyltransferase ( DNMT ) and human DNMT 1 . ^^^ We found that each of the tea polyphenols [ catechin , epicatechin , and ( ) epigallocatechin 3 O gallate ( EGCG ) ] and bioflavonoids ( quercetin , fisetin , and myricetin ) inhibited SssI DNMT and DNMT 1 mediated DNA methylation in a concentration dependent manner . ^^^ In comparison , the strong inhibitory effect of EGCG on DNMT mediated DNA methylation was independent of its own methylation and was largely due to its direct inhibition of the DNMTs . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Increased DNA methyltransferase 1 ( DNMT 1 ) protein expression in precancerous conditions and ductal carcinomas of the pancreas . ^^^ The aim of the present study was to evaluate the significance of DNA methyltransferase 1 ( DNMT 1 ) protein expression during pancreatic carcinogenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In such embryos , the aberrant expression of the somatic isoform of Dnmt 1 ( Dnmt1s ) , the enzyme responsible for maintaining DNA methylation in all somatic cells , has been implicated as one factor in the improper reprogramming of the donor genome . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
SssI DNA methyltransferase ( DNMT ) and human DNMT 1 . ^^^ SssI DNMT mediated DNA methylation , and were 2 . 3 and 0 . 9 microM , respectively , for the inhibition of human DNMT 1 mediated DNA methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To study the regulation of DNA methylation in living cells , we developed a trapping assay using transiently expressed fluorescent DNA methyltransferase 1 ( Dnmt 1 ) fusions and mechanism based inhibitors 5 azacytidine ( 5 aza C ) or 5 aza 2 ' deoxycytidine ( 5 aza dC ) . ^^^ These nucleotide analogs are incorporated into the newly synthesized DNA at nuclear replication sites and cause irreversible immobilization , that is , trapping of Dnmt 1 fusions at these sites . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) deficient mice are tumor prone , and this has been proposed to result from the induction of genomic instability . ^^^ Array based comparative genomic hybridization analyses indicated that double , but not single , DNMT knock out cells display two specific alterations in regional DNA copy number , suggesting that DNMT deficiency and genomic DNA hypomethylation are not associated with widespread genomic amplifications or deletions in human cancer cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Despite decades of nonclinical and clinical research , there remains considerable interest in finding innovative and better ways to use these DNA methyltransferase ( DNMT ) inhibitors . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We constructed RRBS libraries from murine ES cells and from ES cells lacking DNA methyltransferases Dnmt3a and 3b and with knocked down ( kd ) levels of Dnmt 1 ( Dnmt [ 1 ( kd ) , 3a / , 3b / ] ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We report here that procainamide specifically inhibits the hemimethylase activity of DNA methyltransferase 1 ( DNMT 1 ) , the mammalian enzyme thought to be responsible for maintaining DNA methylation patterns during replication . ^^^ At micromolar concentrations , procainamide was found to be a partial competitive inhibitor of DNMT 1 , reducing the affinity of the enzyme for its two substrates , hemimethylated DNA and S adenosyl l methionine . ^^^ By doing so , procainamide significantly decreased the processivity of DNMT 1 on hemimethylated DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Previous work has demonstrated that decreased CpG island methylation in mice lacking the DNA methyltransferase DNMT 1 is associated with impaired tumorigenesis when crossed on the tumour susceptible Apc ( Min / + ) background . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Altered DNA methylation was associated with reduced expression of maintenance ( DNMT 1 ) and , to a lesser extent , de novo DNA methyltransferase DNMT3a in exposed animals . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To understand the chromatin remodeling activities in cloned embryos and to improve NT technology , we examined the expression profiles of five genes involved in DNA and histone modifications , DNMT 1 , DNMT3A , DNMT3B , HAT 1 and HDAC 1 , in single swamp buffalo metaphase 2 oocytes , NT and in vitro fertilized ( IVF ) embryos from the two cell to the blastocyst stage , by quantitative real time RT PCR . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The Bax , E cad , IF tau , Hsp ( heat shock protein ) 70 , Igf2r ( insulin like growth factor 2 receptor ) , DNMT ( DNA methyltransferase ) 1 and Mash ( mammalian achaete scute homologue ) 2 genes were selected for gene expression analysis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have analyzed the relationship between the allosteric regulation and processive catalysis of DNA methyltransferase 1 ( Dnmt 1 ) . ^^^ Our results provide further evidence that the active site and the allosteric sites on Dnmt 1 can bind DNA independently . ^^^ Dnmt 1 ' s processive catalysis on unmethylated DNA is partially inhibited when the allosteric site binds unmethylated DNA and fully inhibited when the allosteric site binds a single stranded oligonucleotide inhibitor . ^^^ Our in vitro results are consistent with the possibility that the processive action of Dnmt 1 may be regulated in vivo by specific regulatory nucleic acids such as DNA , RNA , or poly ( ADP ribose ) . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Association of BMI 1 with polycomb bodies is dynamic and requires PRC2 / EZH2 and the maintenance DNA methyltransferase DNMT 1 . ^^^ Furthermore , we demonstrate that the maintenance DNA methyltransferase DNMT 1 is necessary for proper PcG body assembly independent of DNMT associated histone deacetylase activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Interestingly , more malignant MDA MB 231 human breast cancer cells have a more prominent loss of DNA methylation accompanied by altered expression of maintenance DNA methyltransferase DNMT 1 , methyl binding proteins MeCP 2 and MBD 2 , decreased trimethylation of lysine 20 of histone H 4 and hyperacetylation of histone H 4 compared to MCF 7 cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Recently , we have shown that MT 1 promoter is methylated and suppressed in some solid and liquid tumors and can be robustly activated following treatment with inhibitors of DNA methyltransferase ( DNMT ) and histone deacetylase ( HDAC ) . ^^^ Ubiquitously expressed DNA methyltransferase 1 ( DNMT 1 ) suppressed MT 1 promoter activity irrespective of its methylation status that does not require its catalytic activity . ^^^ These results demonstrate that the methylated and unmethylated MT 1 promoter are differentially regulated by DNA methyltransferase and methyl CpG binding proteins , and DNMT 1 could suppress MT promoter by a transcriptional mechanism independent of its enzymatic function . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here , we show an interaction between PU . 1 and DNA methyltransferases , DNA methyltransferase ( Dnmt ) 3a and Dnmt3b ( Dnmt3s ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Azacitidine ( Vidaza , Pharmion Corp . , Boulder , CO , USA ) and decitabine ( Dacogentrade mark , SuperGen , Inc . , Dublin , CA , USA , and MGI Pharma , Inc . , Bloomington , MN , USA ) are DNA methyltransferase ( DNMT ) inhibitors that have clinical activity in patients with myelodysplastic syndromes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase ( DNMT ) inhibitors azacitidine and decitabine have significant activity in the treatment of MDS . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase ( DNMT ) inhibitors , azacitidine ( Vidaza , Pharmion , Boulder , CO , USA ) and decitabine ( Dacogen ; SuperGen Inc , Dublin , CA , USA , and MGI Pharma Inc , Bloomington , MN , USA ) , have had a significant impact on the treatment paradigm of myelodysplastic syndromes ( MDSs ) , previously managed mainly by supportive care and hematopoietic stem cell transplantation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Recent advances in the investigation of DNMT function in epigenetic DNA changes have formed the basis of the understanding of various disorder etiopathogeneses , and as a result , have facilitated and enabled new therapies with respect to these diseases . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Allele C specific methylation of the 5 HT2A receptor gene : evidence for correlation with its expression and expression of DNA methylase DNMT 1 . ^^^ Methylation of allele C specific CpG sites in the first exon correlated significantly with the expression of DNA methylase 1 ( DNMT 1 ) but not S adenosylhomocysteine hydrolase ( AHCY ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Reprogramming of DNA methylation is an essential part of gametogenesis , and a role of two members of the DNA methyltransferase ( Dnmt ) family , Dnmt3a and Dnmt3L , has been recognized . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) , in particular , is overexpressed in many tumor types . ^^^ Taken together , these data suggest that Dnmt 1 is rapidly activated by pRb pathway inactivation , and that DNA methyltransferase activity is required for malignant transformation and tumorigenesis . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The reproducibility of constructing a cDNA library was tested by five independent PCR experiments with specific primers for the presence of several rare genes such as DNMT 1 ( DNA methylation transferase 1 ) , DNMT 2 , DNMT3A , Oct 4 / 3 ( octmer binding transcription factor ) , IFN iota , IGF 2r ( insulin like growth factor 2 receptor ) , and the housekeeping genes , H2A and beta actin . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A major obstacle toward understanding how patterns of abnormal mammalian cytosine DNA methylation are established is the difficulty in quantitating the de novo methylation activities of DNA methyltransferases ( DNMT ) thought to catalyze these reactions . ^^^ The activity of DNMT 1 against unmethylated CpG rich DNA was further tested by introducing CpG island substrates and DNMT 1 into Drosophila melanogaster cells . ^^^ The exogenous DNMT 1 methylates the integrated mammalian CpG islands but not the Drosophila DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Previous work has shown that DNA hypermethylation of tumor suppressor genes in colorectal cancer cells may be maintained in the absence of the major mammalian methyltransferase , DNA methyltransferase 1 ( DNMT 1 ) . ^^^ These observations suggest that human cancer cells may differ in their reliance on DNMT 1 for maintaining DNA methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
OBJECTIVE : DNA methyltransferase ( DNMT ) 1 , DNMT3b , or both , facilitate malignant transformation through chromatin remodeling mechanisms . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Regional DNA hypermethylation and DNA methyltransferase ( DNMT ) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissues . ^^^ DNA methylation status on CpG islands of the p 16 , human MutL homologue 1 ( hMLH 1 ) , von Hippel Lindau ( VHL ) and thrombospondin 1 ( THBS 1 ) genes and the methylated in tumor ( MINT ) 1 , 2 , 12 , 25 and 31 clones and DNA methyltransferase ( DNMT ) 1 expression were examined by bisulfite modification and immunohistochemistry , respectively . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To directly study the role of DNA methyltransferase 1 ( DNMT 1 ) in the regulation of expression of tumor related genes in human colon cancer cells , we stably transfected expression constructs containing sense or antisense DNMT 1 into the human colon cancer cell line , SW 1116 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We find that the PcG protein EZH 2 ( Enhancer of Zeste homolog 2 ) interacts within the context of the Polycomb repressive complexes 2 and 3 ( PRC2 / 3 ) with DNA methyltransferases ( DNMTs ) and associates with DNMT activity in vivo . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Accuracy of DNA methylation pattern preservation by the Dnmt 1 methyltransferase . ^^^ DNA methyltransferase 1 ( Dnmt 1 ) has a central role in copying the pattern of DNA methylation after replication which is one manifestation of epigenetic inheritance . ^^^ With oligonculeotide substrates we show that mouse Dnmt 1 has a 30 to 40 fold preference for hemimethylated DNA that is almost lost after addition of fully methylated oligonucleotides . ^^^ Dnmt 1 moves along the DNA in a random walk methylating hemimethylated substrates with high processivity ( > 50 sites are visited on average which corresponds to linear diffusion over 6000 bp ) . ^^^ CGCTC sites tend to terminate the processive methylation of DNA by Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To evaluate this hypothesis , we examined common variants in 12 genes coding for DNA methyltransferases ( DNMT ) , histone acetyltransferases , histone deacetyltransferases , histone methyltrasferases and methyl CpG binding domain proteins , for association with breast cancer in a large case control study ( N cases = 4474 and N controls = 4580 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Using an isogenic panel of cell lines proficient or deficient in the DNA methyltransferases ( DNMTs ) DNMT 1 and / or DNMT3B , we show that hypermethylation of the WIF 1 promoter is attributable to the cooperative activity of both DNMT 1 and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Inhibitors of DNA methyltransferases ( DNMT ) and histone deacetylases can reactivate epigenetically silenced tumor suppressor genes and thereby decrease tumor cell growth . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To reverse silencing , 5 AZA deoxycytidine ( 5 AZA dC ) or selective depletion of DNA methyltransferase 1 ( DNMT 1 ) by phosphorothioate oligonucleotide antisense ( DNMT 1 AS ) were employed in cells resistant ( < 5 % terminal deoxynucleotidyl transferase mediated nick end labeling positive ) to apoptosis induction by IFN alpha 2 and IFN beta ( ACHN , SK RC 45 , and A 375 ) . 5 AZA dC and DNMT 1 AS similarly depleted available DNMT 1 protein and , at doses that did not cause apoptosis alone , resulted in apoptotic response to IFNs . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Aging in heterozygous Dnmt 1 deficient mice : effects on survival , the DNA methylation genes , and the development of amyloidosis . ^^^ We previously reported that heterozygous DNA methyltransferase 1 deficient ( Dnmt 1 ( + / ) ) mice maintain T cell immune function and DNA methylation levels with aging , whereas controls develop autoimmunity , immune senescence , and DNA hypomethylation . ^^^ We therefore compared survival , cause of death , and T cell DNA methylation gene expression during aging in Dnmt 1 ( + / ) mice and controls . ^^^ MeCP 2 , a methylcytosine binding protein that participates in maintenance DNA methylation , increased with age in Dnmt 1 ( + / ) mice , suggesting a mechanism for the sustained DNA methylation levels . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Correspondently , the protein levels of DNA methyltransferase 1 ( DNMT 1 ) and DNMT3a increase from young to middle aged fibroblasts but decrease in the senescent fibroblasts , while DNMT3b decreases stably from young to senescent fibroblasts . p 21 ( Waf1 / Cip1 ) promoter methylation directly represses its expression and blocks the radiation induced DNA damage signaling pathway by p 53 in middle aged fibroblasts . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To determine whether DNA methylation can modulate matrix metalloproteinase ( mmp ) gene expression , we have used a genetically engineered cell line in which both key DNA methyltransferase genes , Dnmt 1 and Dnmt 3b , were removed by homologous recombination . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation ( 5 methylcytosine ) in mammalian genomes predominantly occurs at CpG dinucleotides , is maintained by DNA methyltransferase 1 ( Dnmt 1 ) , and is essential for embryo viability . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Intriguingly , however , we observed a significant reduction in the levels of the de novo DNA methyltransferases DNMT3a and 3b and a concurrent increase in the levels of the maintenance DNA methyltransferase DNMT 1 in bystander tissues . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Quantitative analysis of associations between DNA hypermethylation , hypomethylation , and DNMT RNA levels in ovarian tumors . ^^^ How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase ( DNMT ) gene expression is ill defined . ^^^ We used ovarian epithelial tumors of different malignant potential to look for associations between 5 ' gene region or promoter hypermethylation , satellite , or global DNA hypomethylation , and RNA levels for ten DNMT isoforms . ^^^ Our results suggest that there is not a simple association of gene hypermethylation in cancer with altered DNMT RNA levels , and that this hypermethylation is neither the result nor the cause of satellite and global DNA hypomethylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
BACKGROUND & OBJECTIVE : Dnmt 1 , a major DNA methyltransferase gene , is highly expressed in many cancers and lowly expressed in normal adult cells , therefore , its overexpression is closely related to tumorigenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation of multiple tumor related genes in association with overexpression of DNA methyltransferase 1 ( DNMT 1 ) during multistage carcinogenesis of the pancreas . ^^^ These data suggest that accumulation of DNA methylation of multiple tumor related genes is involved in multistage carcinogenesis of the pancreas from early precancerous stages to malignant progression and that DNMT 1 protein overexpression may be responsible for this aberrant DNA methylation . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We recently demonstrated that the DNA methyltransferase 1 ( DNMT 1 ) gene is an E2F target gene that is transcriptionally activated in cells lacking the retinoblastoma gene ( Rb / ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Inhibition of DNA methyltransferase ( Dnmt ) enzymes with 5 aza 2 ' deoxycytidine or genetic ablation of both Dnmt 1 and Dnmt3b prevented promoter methylation and restored CXCL 12 expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Protein expression of Fhit and the DNA methyltransferases ( DNMTs ) DNMT 1 and DNMT3a were assessed by immunoblot analysis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In mammals , CpG methylation patterns are established and maintained during development by the Dnmt 1 and Dnmt 3 families of DNA methyltransferases . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In mammals 3 families of DNA methyltransferases ( MTases ) comprising ( so far ) 4 members have been found : Dnmt 1 , Dnmt 2 , Dnmt3A and Dnmt3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Collectively , our studies suggest that SZ is characterized by a gamma amino butyric acid ( GABA ) ergic neuron pathology presumably mediated by promoter hypermethylation facilitated by the over expression of the methylating enzyme DNA methyltransferase ( Dnmt ) 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Using cre mediated deletion of DNA methyltransferase 1 ( Dnmt 1 ) at the time of CD8+ T cell activation , we investigated the obligation for maintaining patterns of DNA methylation during the generation of Ag specific effector and memory CD8+ T cells in response to acute viral infection of mice with lymphocytic choriomeningitis virus . ^^^ Our data suggest that ablation of Dnmt 1 and subsequent DNA methylation affect the finite proliferative potential of Ag specific CD8+ T cells with moderate effects on their differentiation to effector and memory CD8+ T cells . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this study , we examined the role DNA ( cytosine 5 ) methyltransferase ( DNMT ) activity might play in regulating the induction of synaptic plasticity . ^^^ We found that the DNA within promoters for reelin and brain derived neurotrophic factor , genes implicated in the induction of synaptic plasticity in the adult hippocampus , exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The DNA methyltransferase ( DNMT ) mRNA levels and enzyme activity were also examined . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
RB recruits a number of proteins , including HDACs , SWI / SNF complex , lysine methyl transferase ( SUV39H1 ) and DNA methyltransferase ( DNMT 1 ) , all of which negatively regulate E2F activity with RB . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Protein expressions of maintenance ( DNMT 1 ) DNA methyltransferase and de novo DNA methyltransferases DNMT3a and DNMT3b were decreased at all time points . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Selenium deficiency did not affect DNA methyltransferase ( Dnmt ) activity in liver but tended to decrease ( p < 0 . 06 ) the activity of the enzyme in the colon . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
SETDB 1 interacts with the de novo DNA methyltransferases DNMT3A and DNMT3B but not with the maintenance methyltransferase DNMT 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Exposure to 5 azaC altered the expression of genes involved in imprinting ( IGF 2 ) or pro apoptosis ( BAX ) , whereas there was a reduction in the expression of the main enzyme responsible for replicating the DNA methylation pattern ( DNMT 1 ) and anti apoptosis ( BCL2L1 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We investigated changes in the DNA methylation machinery , namely , de novo DNA methyltransferases ( Dnmt3a and 3b ) , maintenance DNA methyltransferase ( Dnmt 1 ) , and methyl CpG binding proteins ( MBDs ) , in rat livers during early stages of tumorigenesis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Subsequently , the expression levels of the DNA methyltransferases Dnmt 1 , Dnmt3a and Dnmt3b and the transcription factors Sp 1 and Sp 3 , which have been reported to regulate the expression of Dnmts , were examined at days 5 , 14 and 30 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Potent compounds selective for the bacterial target were identified , whereas other compounds showed greater selectivity for the mammalian DNA cytosine methyltransferase , Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dna methyltransferase 1 ( DNMT 1 ) gene activity in human lymphomas correlates with aberrant p 53 gene expression . ^^^ BACKGROUND : The DNA Methyltransferase 1 ( DNMT 1 ) gene has been implicated as a mutagen for tumor suppressor genes by causing hypermethylation and subsequent TA mutations of CpG islands located in the promoter regions of these genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Either 5 AZA dC or an antisense to DNA methyltransferase 1 ( DNMT 1 ) overcame resistance to apoptosis induction by IFNs with up to 85 % apoptotic cells resulting from the combinations . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we show that both Cdc25C and Cdc 2 were down regulated in wild type HCT 116 cells but not in p 53 null , DNMT 1 null or DNMT1and DNMT3b null cells , upon p 53 stabilization following doxorubicin mediated DNA damage . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In addition , disrupting the expression of either one of two DNA methyltransferases ( DNMT 1 or DNMT3B ) by specific siRNAs abolished the siRNA mediated methylation of DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Furthermore , cells treated with IL 6 exhibit an increase in the expression of the DNA maintenance methylation enzyme , DNMT 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Maintenance of self renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt 1 , Dnmt3a and Dnmt3b . ^^^ DNA methyltransferases Dnmt 1 , Dnmt3a and Dnmt3b cooperatively regulate cytosine methylation in CpG dinucleotides in mammalian genomes , providing an epigenetic basis for gene silencing and maintenance of genome integrity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
STAT 3 induces transcription of the DNA methyltransferase 1 gene ( DNMT 1 ) in malignant T lymphocytes . ^^^ In turn , inhibition of DNMT 1 by a small molecule inhibitor , 5 aza 2 deoxy cytidine , and 2 DNMT 1 antisense DNA oligonucleotides inhibits the phosphorylation of STAT 3 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The results from a variety of reporter genes including the splicing factor SRp 20 and the DNA methylase Dnmt 1 suggest that mb 1 cre is probably the best model so far described for pan B cell specific cre expression . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A cellular senescence like phenotype can be induced in immortal LFS cells by treating them with the DNA methyltransferase ( DNMT ) inhibitor 5 aza deoxycytidine . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The loss of DNA methylation was paralleled by a significant decrease in the levels of maintenance ( DNMT 1 ) and de novo methyltransferases DNMT3a and 3b and methyl CpG binding protein MeCP 2 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The methylation of genomic DNA in malignant cells is catalyzed by DNA methyltransferases DNMT 1 and DNMT3B , revealing significantly elevated expression in different types of cancers . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To address this issue , we examined the roles of DNA methyltransferase 1 ( Dnmt 1 ) and the H3K9 histone methyltransferase Suv39h1 in zebra fish development . ^^^ Embryos lacking Suv39h1 had organ specific terminal differentiation defects that produced largely phenocopies of Dnmt 1 morphants but retained wild type levels of DNA methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 1 ( DNMT 1 ) is an important component of the epigenetic machinery and is responsible for copying DNA methylation patterns during cell division . ^^^ Knockdown of DNMT 1 leads to inhibition of DNA replication , but the mechanism has been unclear . ^^^ Here we show that depletion of DNMT 1 with either antisense or small interfering RNA ( siRNA ) specific to DNMT 1 activates a cascade of genotoxic stress checkpoint proteins , resulting in phosphorylation of checkpoint kinases 1 and 2 ( Chk 1 and 2 ) , gammaH2AX focus formation , and cell division control protein 25a ( CDC25a ) degradation , in an ataxia telangiectasia mutated Rad 3 related ( ATR ) dependent manner . siRNA knockdown of ATR blocks the response to DNMT 1 depletion ; DNA synthesis continues in the absence of DNMT 1 , resulting in global hypomethylation . ^^^ There is no response to short term treatment with 5 aza deoxycytidine ( 5 aza CdR ) , which causes demethylation by trapping DNMT 1 in 5 aza CdR containing DNA but does not cause disappearance of DNMT 1 from the nucleus . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development . ^^^ Here we demonstrate that two recently identified DNA methyltransferases , Dnmt3a and Dnmt3b , are essential for de novo methylation and for mouse development . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Overexpression of human DNMT 1 or murine Dnmt3b does not lead to the same pattern or degree of de novo methylation on the episome as overexpression of murine Dnmt3a . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Assignment of cytosine 5 DNA methyltransferases Dnmt3a and Dnmt3b to mouse chromosome bands 12A2 A 3 and 2H1 by in situ hybridization . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We , as well as others , have found that these effects derive from mutations in the DNMT3B DNA methyltransferase gene . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Positional candidate cloning recently discovered the de novo DNA methyltransferase 3B ( DNMT3B ) as the responsible gene by identifying seven different mutations in nine ICF patients . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dnmt3b3 , an isoform of Dnmt3b , did not have DNA methylation activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mutation in the DNMT3B DNA methyltransferase gene is a common cause of ICF ( immunodeficiency , centromeric heterochromatin , facial anomalies ) immunodeficiency syndrome and leads to hypomethylation of satellites 2 and 3 in pericentric heterochromatin . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dnmt3b , de novo DNA methyltransferase , interacts with SUMO 1 and Ubc 9 through its N terminal region and is subject to modification by SUMO 1 . ^^^ Dnmt3b , a DNA methyltransferase , is essential for mammalian development potentially through its transcription repression activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
ICF ( immunodeficiency , centromeric region instability and facial anomalies ) is a recessive disease caused by mutations in the DNA methyltransferase 3B gene ( DNMT3B ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA binding folds . ^^^ The PWWP domain is a weakly conserved sequence motif found in > 60 eukaryotic proteins , including the mammalian DNA methyltransferases Dnmt3a and Dnmt3b . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In this study , we demonstrate that Dnmt3L , a protein sharing homology with DNA methyltransferases , Dnmt3a and Dnmt3b , but lacking enzymatic activity , is essential for the establishment of maternal methylation imprints and appropriate expression of maternally imprinted genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mouse DNA ( cytosine 5 ) methyltransferases Dnmt3a and Dnmt3b are expected to be de novo type DNA methyltransferases . ^^^ On the other hand , neither bacterial DNA ( cytosine 5 ) methyltransferase nor Dnmt3b3 , one of the three isoforms of Dnmt3b that has no DNA methylation activity , induced apoptosis . ^^^ In addition , mutant Dnmt3a and the other two Dnmt3b isoforms , Dnmt3b1 and Dnmt3b2 , which have no DNA methylation activity due to a change of the cysteine residue in the catalytic center to an alanine residue , retained the ability to induce apoptosis . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
When beta actin was used as an internal control , the mRNA expression of three DNMTs ( DNMT 1 , DNMT3A , and DNMT3B ) and five MBPs ( MBD 1 , MBD 2 , MBD 3 , MBD 4 , and MeCP 2 ) was upregulated in SCLC , while only that of DNMT 1 , DNMT3B and MBD 3 was upregulated in NSCLC , compared with normal lung tissues . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A DNA methyltransferase , DNMT3b , is required for methylation on pericentromeric satellite regions during mouse development . ^^^ To clarify the molecular mechanism underlying DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis , we examined mutations of the DNMT3b gene and mRNA expression levels of splice variants of DNMT3b in noncancerous liver tissues showing chronic hepatitis and cirrhosis , which are considered to be precancerous conditions , and in hepatocellular carcinomas ( HCCs ) . ^^^ Overexpression of DNMT3b4 , a splice variant of DNMT3b lacking conserved methyltransferase motifs 9 and 10 , significantly correlated with DNA hypomethylation on pericentromeric satellite regions in precancerous conditions and HCCs ( P = 0 . 0001 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNMT3L shows high similarity to the de novo DNA methyltransferases , DNMT3A and DNMT3B , however , the amino acid residues needed for DNA cytosine methyltransferase activity have been lost from the DNMT3L protein sequence . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
ICF syndrome ( immunodeficiency , centromere instability and facial anomalies ) is a recessive human genetic disorder resulting from mutations in the DNA methyltransferase 3B ( DNMT3B ) gene . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Recently , we identified a C > T transition at a novel promoter region of cytosine DNA methyltransferase 3B ( DNMT3B ) and found that this polymorphic transition significantly increases the promoter activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
It is caused by mutations in a de novo DNA methyltransferase gene , DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Two DNA methyltransferases , Dnmt3a and Dnmt3b , contribute to the creation of DNA methylation patterns in embryos . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The DNA methyltransferases ( MTases ) Dnmt3a and Dnmt3b are thought to be the sole de novo MTases in the mammalian genome . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
While DNMT 1 is thought to perform maintenance methylation , the more recently discovered DNMT3a and DNMT3b enzymes are thought to facilitate de novo methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
RESULTS : The cDNA isolated in our hands was one of the alternative splicing isoforms of mouse de novo DNA cytosine 5 ' specific methyltransferase gene ( Dnmt3b ) reported in July , 1998 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
ICF patients have constitutive hypomethylation at satellite 2 DNA ( Sat 2 ) in 1qh and 16qh , generally as the result of mutations in the DNA methyltransferase gene DNMT3B . ^^^ DNMT 1 , DNMT3A , or DNMT3B RNA levels did not differ significantly between CV and AF cultures or late and early passages . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To analyse the protein structure and consequences of ICF causing mutations , we modelled the structure of the DNMT3B methyltransferase domain based on Haemophilus haemolyticus protein in complex with the cofactor AdoMet and the target DNA sequence . ^^^ Based on the model , the DNMT3B recognizes the GC sequence and flips the cytosine from the double stranded DNA to the catalytic pocket . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The Dnmt3b gene encodes a de novo DNA methyltransferase that is essential for normal mouse development . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Comparison to the recently reported structure of a homologous domain from the mammalian DNA methyltransferase Dnmt3b reveals substantial differences both in the C terminal helical region and in the PWWP motif . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
RESULTS : Here , we demonstrate a physical and functional link between the Suv39h HP 1 histone methylation system and DNA methyltransferase 3b ( Dnmt3b ) in mammals . ^^^ While the Suv39h HMTases are required to direct H 3 K9 trimethylation and Dnmt3b dependent DNA methylation at pericentric repeats , DNA methylation at centromeric repeats occurs independent of Suv39h function . ^^^ In contrast , H 3 K9 trimethylation at pericentric heterochromatin is not impaired in Dnmt 1 single or Dnmt3a / Dnmt3b double deficient ES cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Distinct enzymatic properties of recombinant mouse DNA methyltransferases Dnmt3a and Dnmt3b . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we show that a de novo DNA methyltransferase , DNMT3b , substantially contributes to the oncogenic phenotype in a lung cancer model . ^^^ While expression of TSCL 1 correlated with methylation of CpG dinucleotides in its promoter region , the expression of FHIT did not , suggesting that DNMT3b may silence genes by several mechanisms including direct DNA methylation or recruitment of proteins that modify chromatin . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mutations in the DNMT3B DNA methyltransferase gene cause the ICF immunodeficiency syndrome . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Cells from ICF patients who are deficient in one of the DNA methyltransferases , DNMT3B , provide an opportunity to explore and refine this hypothesis . ^^^ The DNMT3B methyltransferase , therefore , is required for methylation of L 1 CpG islands on the inactive 10 , whereas methylation of the corresponding L 1 loci on the active 10 , as well as most autosomal L1s , is accomplished by another DNA methyltransferase . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Most of these proteins fall into two distinct chromosomal distribution patterns : ( a ) kinetochore associated proteins ( Sin3A , PCAF , MYST and BAF 180 ) , which colocalize with metaphase kinetochores , but not any of the pericentric and other major heterochromatic regions ; and ( b ) heterochromatin associated proteins ( MeCP 2 , MBD 1 , MBD 2 , ATRX , HP1alpha , HDAC 1 , HDAC 2 , DNMT 1 and DNMT3b ) , which colocalize with centromeric / pericentric heterochromatin and all other major heterochromatic sites . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
This review summarizes our knowledge about the immunological symptoms of ICF ; the nature of DNMT3B mutations in ICF patients ; the phenotypes of DNA hypomethylation mutants in humans , mice , and Arabidopsis ; the epigenetics of ICF ; and ICF specific RNA expression and cell surface antigen expression in lymphoblastoid cell lines . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mutations in the DNA methyltransferase 3B ( DNMT3B ) gene are responsible for most ICF cases reported . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Two de novo DNA methyltransferases , Dnmt3a and Dnmt3b , are responsible for the process . ^^^ The functional significance of PWWP mediated chromatin targeting is suggested by the fact that a missense mutation in this domain of human DNMT3B causes immunodeficiency , centromeric heterochromatin instability , facial anomalies ( ICF ) syndrome , which is characterized by loss of methylation in satellite DNA , pericentromeric instability , and immunodeficiency . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We also found conserved cytoplasmic polyadenylation elements , usually implicated in regulating translation in oocytes , in Dnmt3b and Dnmt 1 . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Although de novo DNA methyltransferases of the Dnmt 3 family are implicated in maternal imprinting , the lethality of Dnmt3a and Dnmt3b knockout mice has precluded further studies . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The DNMT3A ( DNA methyltransferase 3A ) and DNMT3B genes encode putative de novo methyltransferases and show complex transcriptional regulation in the presence of three and two different promoters respectively . ^^^ The importance of these Sp 1 binding sites was demonstrated by using a GC rich DNA binding protein inhibitor , mithramycin A , i . e . on the basis of decrease in the promoter activities and mRNA expression levels of DNMT3A and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In ICF cells , however , genes subject to 10 inactivation are hypomethylated on the inactive 10 due to mutations in the DNA methyltransferase ( DNMT3B ) genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin . ^^^ Dnmt3a and Dnmt3b are responsible for the establishment of DNA methylation patterns during development . ^^^ Furthermore , we demonstrate that the Dnmt3a PWWP domain has little DNA binding ability , in contrast to the Dnmt3b PWWP domain , which binds DNA nonspecifically . ^^^ Collectively , our results suggest that the PWWP domains of Dnmt3a and Dnmt3b are essential for targeting these enzymes to pericentric heterochromatin , probably via a mechanism other than protein DNA interactions . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The Immunodeficiency , Centromeric instability , and Facial ( ICF ) syndrome is a rare autosomal recessive disorder that results from mutations in the DNMT3B gene , encoding a DNA methyltransferase that acts on GC rich satellite DNAs . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We present the data on tissue specificity in radiation induced expression of DNA methyltransferases , and prove that changes in the expression of de novo methyltransferases DNMT3a and DNMT3b are the most important in radiation induced DNA methylation alterations . ^^^ In the current study , we examined the radiation induced changes in expression of maintenance DNMT 1 , and de novo methyltransferases DNMT3a and DNMT3b in spleen and liver of irradiated animals . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 3B ( DNMT3B ) plays an important role in the generation of aberrant methylation in carcinogenesis . ^^^ Polymorphisms and haplotypes of the DNMT3B gene may influence DNMT3B activity on DNA methylation , thereby modulating the susceptibility to lung cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Two de novo type DNA methyltransferases , Dnmt3a and Dnmt3b , are responsible for the creation of DNA methylation patterns during development . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Both mRNA and protein levels of Dnmt 1 and Dnmt3b were increased in the thymus and the liver of p 53 deficient mice . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In the present study , we examined which de novo type DNA methyltransferase , Dnmt3a , Dnmt3a2 or Dnmt3b is expressed in gonocytes at these stages . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNMT3B mutations and DNA methylation defect define two types of ICF syndrome . ^^^ Mutations in the catalytic domain of DNMT3B , a gene encoding a de novo DNA methyltransferase , have been recognized in a subset of patients . ^^^ The variable incidence of DNMT3B mutations and the differential methylation defect of alpha satellites allow the identification of two types of patients , both showing an undermethylation of classical satellite DNA . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The mRNA and protein levels of de novo methyltransferase Dnmt3b increased , whereas those of Dnmt3a and Dnmt 1 decreased , during NGF induced neurite outgrowth . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
OBJECTIVE : To understand the role of epigenetic regulation in the pathogenesis of endometrial cancer , we have characterized DNA methyltransferase 3B ( DNMT3B ) gene expression in normal , Grade 1 and Grade 3 endometrioid cancers , and examined DNMT3B promoter activities in endometrial cancer cell lines . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA ( cytosine C 5 ) methyltransferases by Dnmt3L . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system . ^^^ To explore the role of DNA methylation in the brain , we examined the expression pattern of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the mouse central nervous system ( CNS ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The expression of de novo DNA methylase DNMT3b , of the methyl CpG binding protein MBD2b and of 5 MCDG glycosylase shows two waves of induction during CaCO 2 cell differentiation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyltransferases shape the human epigenome . ^^^ We have investigated the influence of flanking sequence on the catalytic activity of the Dnmt3a and Dnmt3b de novo DNA methyltransferases using a set of synthetic oligonucleotide substrates that covers all possible + / 1 flanks in quantitative terms . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Of particular interest , we found that both DNMT3B ( DNA ( cytosine 5 ) methyltransferase 3 beta ) and DNMT3L ( DNA ( cytosine 5 ) methyltransferase 3 like ) were overexpressed in the N SEMs , indicating the epigenetic differences between N SEMs and classical SEM . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
To further elucidate the mechanism by which DNMT3L stimulates DNA methylation , we have mapped in detail the domains that mediate interaction of human DNMT3L with human DNMT3A and DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
AIM : To investigate the association between single nucleotide polymorphism ( SNP ) in promoter of the DNA methyltransferase 3B ( DNMT3B ) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma ( GCA ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A C / T polymorphism in the DNA methyltransferase 3b ( DNMT3b ) promoter region results in increased activity and has recently been identified as a risk factor for lung cancer . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Moreover , expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b was essential for repression and DNA methylation of the Ant 4 gene during ESC differentiation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The aim of this study was to analyze the expression patterns of DNMT 1 , DNMT 2 , DNMT3A , DNMT3B , and DNMT3L genes in rhesus macaque ( Macaca mulatta ) oocytes and preimplantation stage embryos from fertilization to the hatched blastocyst stage , and to compare these results with the expression profiles in the mouse and other mammalian species . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The silencing of GADD45G could be reversed by 5 aza 2 ' deoxycytidine or genetic double knockout of DNMT 1 and DNMT3B , indicating a direct epigenetic mechanism . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
MNB cells overexpressing DNA methyltransferase activity ( Dnmt3a or Dnmt3b ) were established by stable co transfection of wild type MNB cells with plasmids containing Dnmt3a or Dnmt3b cDNA . ^^^ Cytotoxic response ( IC 50 ) , total DNA methyltransferase activity and expression of Dnmt3a or Dnmt3b methyltransferase were determined in Dnmt3a or Dnmt3b transfected MNB cells , respectively . ^^^ RESULTS : These data demonstrated that total DNA methyltransferase activity was increased to 3 fold above controls ( P < 0 . 001 ) in cisplatin resistant MNB cells , 3 fold in Dnmt3a and 4 fold in Dnmt3b transfected MNB cells . ^^^ Incubation of cisplatin resistant , Dnmt3a or Dnmt3b overexpressing MNB cells with 5 ' azacytidine ( 5 ' azaC ) , a methylation inhibitor ( 2 . 5 microM ) significantly decreased DNA methyltransferase activity , expression of Dnmt3a and Dnmt3b proteins and mRNA levels of cisplatin resistant , Dnmt3a and Dnmt3b transfected MNB cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Finally , we show that hypomethylation is associated with reduced levels of the de novo DNA methyltransferases Dnmt3a and Dnmt3b and that ectopic expression of these factors restores global methylation levels . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The transcriptional silencing of PCDH 10 could be reversed by pharmacologic demethylation with 5 aza 2 ' deoxycytidine or genetic demethylation with double knockout of DNMT 1 and DNMT3B , indicating a direct epigenetic mechanism . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dnmt3a and Dnmt3b are de novo DNA methyltransferases that also act as transcriptional repressors independent of methyltransferase activity . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Two types of methylation pathways have been distinguished : maintenance methylation by Dnmt 1 occurring at the replication fork , and de novo methylation established by the methyltransferases Dnmt3a and Dnmt3b . ^^^ Finally , we demonstrate that Lsh associates with Dnmt3a or Dnmt3b but not with Dnmt 1 in embryonic cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Dnmt3a and Dnmt3b are two major de novo DNA methyltransferases essential for embryonic development in mammals . ^^^ However , the exact target CpG sites where Dnmt3a and Dnmt3b catalyze DNA methylation remains largely unknown . ^^^ To identify a CpG site that is specifically methylated by Dnmt3a or Dnmt3b , we screened methylated genomic loci by methylation sensitive restriction fingerprinting using genomic DNA from wild type , Dnmt3a null , Dnmt3b null , and Dnmt3a Dnmt3b double null ES cells . ^^^ Exogenous expression of Dnmt3a but not Dnmt3b in the double null ES cells restored DNA methylation of this CpG site . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methyltransferase 3b ( DNMT3b ) , an enzyme that participates in the establishment of de novo methylation patterns , is highly expressed in many tumor cells and tissues , and it is closely associated with hypermethylation of the promoter of tumor suppressor genes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We found that down regulation of DNMT 1 , but not of DNMT3A and DNMT3B , induces activation of the MAGE A 1 transgene , suggesting that DNMT 1 has a predominant role for methylation maintenance in MZ 2 MEL cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In contrast to SYBL 1 , the inactive 10 and Y alleles of SPRY 3 are not reactivated in cells treated with a DNA methylation inhibitor and in cells from ICF ( immunodeficiency , centromeric instability , facial anomalies ) syndrome patients , which have mutations in the DNA methyltransferase gene DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
ICF ( Immunodeficiency , Centromeric instability and Facial anomalies ) syndrome is a rare autosomal recessive disease caused by mutations in the DNA methyltransferase gene DNMT3B . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Previously we showed that DNA methyltransferase 3b ( Dnmt3b ) is required for nerve growth factor ( NGF ) induced differentiation of PC 12 cells to neuronal phenotype . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L . ^^^ Deficiency in DNA methyltransferase DNMT3B causes a recessive human disorder characterized by immunodeficiency , centromeric instability and facial anomalies ( ICF ) in association with defects in genomic methylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Mouse embryonic stem ( ES ) cells genetically deficient for DNMT 1 , or both DNMT3a and DNMT3b have dramatically elongated telomeres compared with wild type controls . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
ICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes ( DNMT3B ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We compared the temporal expression patterns of the postulated de novo DNA methyltransferases DNMT3a and DNMT3b in murine male germ cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Immunofluorescence analysis and biochemical fractionation showed that all three DNMTs ( DNMT 1 , DNMT3A , and DNMT3B ) are associated with the inactive rDNA in the nucleolus . ^^^ The rDNA primary transcript level was significantly elevated in DNMT 1 / or DNMT3B / human colon carcinoma ( HCT 116 ) cells . ^^^ Transient overexpression of DNMT 1 or DNMT3B suppressed the luciferase expression from both methylated and unmethylated pHrD IRES Luc , a reporter plasmid where the rDNA promoter drives luciferase expression . ^^^ Unlike DNMT 1 , both the wild type and catalytically inactive DNMT3B mutant can suppress rDNA promoter irrespective of its methylation status . ^^^ These results demonstrate localization of DNMTs with the inactive rDNA in the nucleolus , the specific role of DNMT 1 and DNMT3B in rDNA expression and the differential regulation of rDNA expression from the methylated and unmethylated rDNA promoters . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
RESULTS : The mRNA levels of DNMT 1 and DNMT3b were elevated in 53 % and 58 % of 102 NSCLCs , respectively . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
One hundred and thirty two RNA samples obtained from de novo adult AML patients were tested for FLT 3 , FLT 3 LG , NDST 1 , HDAC 2 , ATRX , FOS , DNMT 1 , DNMT3A , DNMT3B , NBS 1 , RAD 50 , MRE11A , Meis 1 and Meis 2 expression using quantitative PCR ( qPCR ) assays . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Rather , in vitro analysis indicates that Dnmt3L stimulates DNA methylation by both Dnmt3a and Dnmt3b through direct binding to these proteins . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We have investigated the distribution of DNA methylation in chromosomes and nuclei of normal individuals and ICF ( Immunodeficiency , Centromeric instability and Facial abnormalities ) syndrome patients , using 5 methylcytosine monoclonal antibody . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
An embryonic like methylation pattern of classical satellite DNA is observed in ICF syndrome . ^^^ When ICF DNA was tested with methyl sensitive enzymes , several classical satellite families , but not alphoid sequences , showed a very low level of methylcytosine in leukocyte DNA , with an abnormal pattern compared to the normal germinal and extraembryonic methylation profile . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
We found that conditioned medium from ICF exposed cultures stimulated [ 3H ] TdR incorporation into DNA , and [ 3H ] proline incorporation into collagenase digestible protein but not into non collagen protein in fresh calvarial cultures . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA , FISH and complementation studies in ICF syndrome : DNA hypomethylation of repetitive and single copy loci and evidence for a trans acting factor . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The overlap of the spectrum of chromosomal rearrangements in azaCR or azaCdR treated FLEB 14 cells and in mitogen stimulated lymphocytes from patients with a rare genetic disease ( ICF ) associated with localized DNA hypomethylation supports the hypothesis that the DNA demethylating activity of azaCR is essential for the induction of these pericentromeric rearrangements . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation in normal individuals and in ICF patients : heterogeneous methylation of constitutive heterochromatin in adult and fetal tissues . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The methylation profile exhibited in ICF patients reproduces the normal profile of placental or sperm DNA . ^^^ The DNA methylation defect in ICF patients , first detected in satellite DNAs ( constitutive heterochromatin ) and CpG islands of genes on the inactive 10 chromosome ( facultative heterochromatin ) , thus includes Alu sequences that are widely distributed throughout the human genome . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
A major component of the pericentromeric DNA in chromosome 1 , satellite 2 , was shown to be hypomethylated in an ICF B cell line , although DNA from this cell line did not display detectable overall hypomethylation . ^^^ It is hypothesized that demethylation in certain DNA regions , including in pericentromeric satellite DNA , helps lead to pericentromeric chromosomal rearrangements in lymphocytes from ICF patients and in normal lymphoblastoid cells incubated in vitro with DNA demethylating agents . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Drug induced DNA demethylation in normal human cells and inherited localized hypomethylation in mitogen stimulated lymphocytes from patients with a rare recessive disease ( ICF : immunodeficiency , centromeric region instability , facial anomalies ) are associated with karyotypic instability . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
ICF patients show marked hypomethylation of their DNA ; undermethylation of classical satellites 2 and 3 is thought to be associated with the centromere instability . ^^^ We used DNA from three consanguineous families with a total of four ICF patients and performed a total genome screen , to localize the ICF syndrome gene by homozygosity mapping . ^^^ Isolation of the gene associated with the ICF syndrome not only will give insight into the etiology of the ICF syndrome but will also broaden our understanding of DNA methylation processes . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Rearrangements in these regions and hypomethylation of satellite 2 DNA are a characteristic feature of patients with a rare recessive genetic disease , ICF ( immunodeficiency , centromeric region instability , and facial anomalies ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA undermethylation is a characteristic feature of ICF syndrome and has been implicated in the formation of the juxtacentromeric chromosomal abnormalities of this rare syndrome . ^^^ Our results suggest that the genetic alteration of DNA methylation in ICF syndrome has little consequence on 10 chromosome gene expression and chromatin organization . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Classical satellite DNA is normally heavily methylated at cytosine residues , but in ICF syndrome it is almost completely unmethylated in all tissues . ^^^ Here we show that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B ( refs 5 , 6 ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Whole genome methylation scan in ICF syndrome : hypomethylation of non satellite DNA repeats D4Z4 and NBL 2 . ^^^ The ICF ( immunodeficiency , centromeric instability and facial abnormalities ) syndrome is a rare recessive disease characterized by immunodeficiency , extraordinary instability of certain heterochromatin regions and mutations in the gene encoding DNA methyltransferase 3B . ^^^ However , ICF DNA digests prominently displayed multicopy fragments absent in controls . ^^^ The high degree of methylation of D4Z4 that we observed in normal cells may be related to the postulated role of this DNA repeat in position effect variegation in facio scapulohumeral muscular dystrophy and might also pertain to abnormal gene expression in ICF . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients . ^^^ The ICF syndrome ( immunodeficiency , centromeric region instability , facial anomalies ) is a unique DNA methylation deficiency disease diagnosed by an extraordinary collection of chromosomal anomalies specifically in the vicinity of the centromeres of chromosomes 1 and 16 ( Chr 1 and Chr 16 ) in mitogen stimulated lymphocytes . ^^^ The ICF specific hypomethylation occurs in only a small percentage of the genome , e . g . , ICF brain DNA had 7 % less 5 methylcytosine than normal brain DNA . ^^^ The ICF lymphoblastoid cell lines , therefore , retain not only the ICF specific pattern of chromosome rearrangements , but also of targeted DNA hypomethylation . ^^^ This hypomethylation of heterochromatic DNA sequences is seen in many cancers and may predispose to chromosome rearrangements in cancer as well as in ICF . . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Immunodeficiency , centromeric region instability , and facial anomalies ( ICF ) , a rare recessive chromosome instability syndrome , involves the loss of DNA methyltransferase 3B activity and the consequent hypomethylation of a small portion of the genome . ^^^ ICF associated undermethylation of some regulatory gene ( s ) might lead to an exaggerated response to radiation induced breaks in DNA yielding increased rates of cell death and irreversible cell cycle arrest . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
DNA methylation has recently moved to centre stage in the aetiology of human neurodevelopmental syndromes such as the fragile 10 , ICF and Rett syndromes . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Satellite DNA hypomethylation has been postulated as the mechanism underlying the induction of chromosome 1 peri centromeric instability in many human cancers and in individuals with the rare recessive disorder ICF ( immunodeficiency , centromeric heterochromatin instability , facial anomalies ) . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Like repeated DNA sequences in the juxtacentromeric heterochromatin of chromosomes 1 , 9 , and 16 , D4Z4 was hypomethylated at numerous CpGs in sperm and in cell lines from patients with an unrelated DNA methyltransferase deficiency syndrome ( ICF ; immunodeficiency , centromeric region instability , facial anomalies ) in contrast to its hypermethylation in non ICF postnatal somatic tissues . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
The immunodeficiency , centromeric region instability , facial anomalies ( ICF ) syndrome , a rare recessive DNA methyltransferase deficiency disease , results in a small decrease in the extent of global genomic methylation . ^^^ In ICF , DNA hypomethylation is targeted to the satellite DNA in juxtacentromeric ( centromere adjacent ) heterochromatin of chromosomes 1 and 16 ( 1qh and 16qh ) , which are prone to rearrangements in ICF lymphoid cells . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
In ICF syndrome , a human disease affecting DNA methylation , SYBL 1 escapes from silencing and this correlates with altered patterns of histone methylation and acetylation . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Previously , it was shown that NBL 2 , a complex tandem DNA repeat in the acrocentric chromosomes , is hypomethylated at NotI sites in > 70 % of neuroblastomas and hepatocellular carcinomas and in cells from ICF syndrome ( DNMT3B deficiency ) patients . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
Here we show that in lymphoblastoid cell lines from four ICF patients , there was increased colocalization of the hypomethylated 1qh and 16qh sequences in interphase , abnormal looping of pericentromeric DNA sequences at metaphase , formation of bridges at anaphase , chromosome 1 and 16 fragmentation at the telophase interphase transition , and , in apoptotic cells , micronuclei with overrepresentation of chromosome 1 and 16 material . ^^^
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9UBC3 and P26358 Pubmed SVM Score :0.0
NA