Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.93119013
Here , we show that Dnmt3a associates with RP 58 , a DNA binding transcriptional repressor protein found at transcriptionally silent heterochromatin . 0.93119013^^^ These results identify Dnmt3a as a co repressor protein carrying deacetylase activity and show that Dnmt3a can be targeted to specific regulatory foci via its association with DNA binding transcription factors . . 0.8397954^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.70094589
Complex formation between Dnmt3A and Dnmt3L accelerates DNA binding by Dnmt3A 20 fold and lowers its K ( m ) for DNA . 0.70094589^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Recently identified new DNA methyltransferase ( DNMT ) genes , DNMT3A and DNMT3B , code for de novo methyltransferases . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Dnmt3b3 , an isoform of Dnmt3b , did not have DNA methylation activity . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
An essential role for DNA methyltransferase DNMT3B in cancer cell survival . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
It is caused by mutations in a de novo DNA methyltransferase gene , DNMT3B . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The Dnmt3b gene encodes a de novo DNA methyltransferase that is essential for normal mouse development . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Distinct enzymatic properties of recombinant mouse DNA methyltransferases Dnmt3a and Dnmt3b . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Mutations in the DNMT3B DNA methyltransferase gene cause the ICF immunodeficiency syndrome . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Mutations in the DNA methyltransferase 3B ( DNMT3B ) gene are responsible for most ICF cases reported . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Expression of another de novo DNA methyltransferase DNMT3b was decreased only in males . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
These findings suggest that Dnmt3a and Dnmt3a2 may have distinct DNA targets and different functions in development . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Overexpression of Dnmt3A or Dnmt3B , which do not interact with PCNA , yielded weaker effects on clonogenicity . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Here we show that Myc binds the corepressor Dnmt3a and associates with DNA methyltransferase activity in vivo . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
In this study , we report that Fo and MZ B cells express different levels of DNA methyltransferase Dnmt3a . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNA hypomethylation has also been associated with abnormal chromosomal structures , as observed in cells from patients with ICF ( Immunodeficiency , Centromeric instability and Facial abnormalities ) syndrome and in cells treated with the demethylating agent 5 azadeoxycytidine . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The recent cloning of a new family of DNA methyltransferases ( Dnmt3a and Dnmt3b ) in mouse which methylate hemimethylated and unmethylated templates with equal efficiencies make them candidates for the long sought de novo methyltransferases . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Recently , two new mammalian DNA methyltransferase genes have been identified , which are referred to as DNMT3A and DNMT3B . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome . ^^^ By searching for homologies to known DNA methyltransferases , we identified a genomic sequence in the ICF region that contains the homologue of the mouse Dnmt3b methyltransferase gene . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
A human genetic disorder ( ICF syndrome ) has recently been shown to be caused by mutations in the DNA methyltransferase 3B ( DNMT3B ) gene . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Although enzymes have been identified that can methylate DNA de novo ( Dnmt3a and Dnmt3b ) ( 14 ) , it is unknown how specific patterns of methylation are established in the genome . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The subcellular distribution of the recently discovered de novo DNA methyltransferases , Dnmt3a and Dnmt3b , was investigated by immunofluorescence and by epitope tagging . ^^^ We now show that both Dnmt3a and Dnmt3b are distributed throughout the nucleoplasm but are not associated with nuclear DNA replication sites during S phase . ^^^ These results suggest that de novo methylation by Dnmt3a and Dnmt3b occurs independently of the replication process and might involve an alternative mechanism for accessing the target DNA . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNA methyltransferase 3B mutations linked to the ICF syndrome cause dysregulation of lymphogenesis genes . ^^^ ICF ( immunodeficiency , centromeric region instability and facial anomalies ) is a recessive disease caused by mutations in the DNA methyltransferase 3B gene ( DNMT3B ) . ^^^ ICF ( immunodeficiency , centromeric region instability and facial anomalies ) is a recessive disease caused by mutations in the DNA methyltransferase 3B gene ( DNMT3B ) . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases . ^^^ 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 . ^^^ However , the catalytic domain of Dnmt3a methylates DNA in a distributive reaction , whereas Dnmt3b is processive , which accelerates methylation of macromolecular DNA in vitro . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNA methyltransferases , Dnmt3a and Dnmt3b , are required for de novo methylation in embryonic stem ( ES ) cells and postimplantation embryos . ^^^ In this study , we have analyzed the sequence specificity of Dnmt3a and Dnmt3b during de novo methylation of murine Moloney leukemia virus provirus DNA in virus infected ES cells . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNA methylation regulates important biological processes and is involved in tumorigenesis and several human diseases , such as Rett and immunodeficiency , centromeric instability and facial anomalies ( ICF ) . ^^^ In search of enzymes responsible for de novo methylation , we have cloned a novel family of mammalian DNA methyltransferase genes , Dnmt3a and Dnmt3b . ^^^ Additionally , biochemical analysis revealed that , unlike Dnmt 1 , neither Dnmt3a nor Dnmt3b had a strong preference to hemimethylated DNA substrates . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells . ^^^ ICF syndrome ( immunodeficiency , centromere instability and facial anomalies ) is a recessive human genetic disorder resulting from mutations in the DNA methyltransferase 3B ( DNMT3B ) gene . ^^^ Global levels of DNA methylation in ICF cells are only slightly reduced ; however , certain repetitive sequences and genes on the inactive 10 chromosome of female ICF patients are significantly hypomethylated . ^^^ Lastly , no consistent changes in the protein levels of the DNA methyltransferases were noted when normal and ICF cell lines were compared . . ^^^ 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Two DNA methyltransferases , Dnmt3a and Dnmt3b , contribute to the creation of DNA methylation patterns in embryos . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^ 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Following purification , the majority of de novo DNA methyltransfearse activity was associated with Dnmt3b / Dnmt1 fractions . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
We have previously shown that the DNA methyltransferases Dnmt3a and Dnmt3b carry out de novo methylation of the mouse genome during early postimplantation development and of maternally imprinted genes in the oocyte . ^^^ In the present study , we demonstrate that Dnmt3a and Dnmt3b are also essential for the stable inheritance , or `` maintenance , ' ' of DNA methylation patterns . ^^^ We also show that hypermethylation of genomic DNA by Dnmt3a and Dnmt3b is necessary for ES cells to form teratomas in nude mice . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The ICF syndrome , a DNA methyltransferase 3B deficiency and immunodeficiency disease . ^^^ These rearrangement prone regions show DNA hypomethylation in all examined ICF cell populations . ^^^ 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 . ^^^ Comparisons of ICF and control lymphoblastoid cell lines and ICF patients ' symptoms suggest an involvement of DNA methylation in the late stages of lymphocyte maturation . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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 . ^^^ Two de novo DNA methyltransferases , Dnmt3a and Dnmt3b , are responsible for the process . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction . ^^^ Two DNA methyltransferases , Dnmt3a and Dnmt3b , are responsible for the creation of DNA methylation patterns . ^^^ In the present study , the effect of DNMT3L , a human homologue of Dnmt3L , on the DNA methylation activity of mouse Dnmt3a and Dnmt3b was examined in vitro . ^^^ 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 . ^^^ DNMT3L could not bind to DNA but could bind to Dnmt3a and Dnmt3b , indicating that the stimulatory effect of DNMT3L on the DNA methylation activity may not be due to the guiding of Dnmt3a and Dnmt3b to the targeting DNA sequence but may comprise a direct effect on their catalytic activity . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
De novo DNA methyltransferase DNMT3B is critical for embryonic development and is mutated in ICF syndrome . ^^^ Here we demonstrate that DNMT3B associates with four chromatin associated enzymatic activities common to transcriptionally repressed , heterochromatic regions of the genome : DNA methyltransferase , histone deacetylase , ATPase , and histone methylase activities . ^^^ Our results therefore link DNMT3B to three other components of the epigenetic machinery and provide important insights into how DNA methylation patterns may be established within the chromatin environment . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The de novo DNA methyltransferase DNMT3B is of particular interest because it is frequently overexpressed in tumor cells and is mutated in immunodeficiency , centromere instability and facial anomalies ( ICF ) syndrome . ^^^ Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
It remains unclear , however , exactly how chromatin and epigenetic chromatin modifications affect the biological properties of the DNA methyltransferases ( DNMT 1 , DNMT3A , and DNMT3B ) . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
ICF syndrome in a girl with DNA hypomethylation but without detectable DNMT3B mutation . ^^^ A 3 year old girl with phenotypic and cytogenetic manifestations of the ICF syndrome and DNA hypomethylation but without DNMT3B gene mutation is described . ^^^ ICF syndrome in a girl with DNA hypomethylation but without detectable DNMT3B mutation . ^^^ Hypomethylation of classical satellite 2 DNA was observed with BstBI digestion , but in a lesser degree than those in the individuals with proven DNMT3B mutations . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^ Therefore , if DNA methylation is upstream of histone modification , the histones on the inactive 10 in ICF cells should not be modified to a silent form . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^ In order to investigate the effect of DNA hypomethylation on heterochromatin organization , we analyzed the in vivo distribution of HP 1 proteins , essential components of heterochromatin , in three ICF patients . ^^^ Finally , satellite DNA length polymorphism could affect the efficiency of heterochromatin condensation and thus contribute to the variability of the ICF phenotype . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNMT3B mutations and DNA methylation defect define two types of ICF syndrome . ^^^ 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
De novo DNA methyltransferases Dnmt3a and Dnmt3b primarily mediate the cytotoxic effect of 5 aza 2 ' deoxycytidine . ^^^ These results suggest that the cytotoxic effect of 5 aza dC may be mediated primarily through Dnmt3a and Dnmt3b de novo DNA methyltransferases . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation , chromosomal instability , and spontaneous immortalization . ^^^ In this study , we have investigated how targeted disruption of the DNA methyltransferases Dnmt3a and Dnmt3b affects the growth of mouse embryonic fibroblasts ( MEFs ) . ^^^ 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 . ^^^ These results suggest that DNA hypomethylation may induce genomic instability , which in turn leads to spontaneous immortalization or premature senescence of Dnmt3b deficient MEFs via a p 53 independent mechanism . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Here we describe a mechanism by which HDAC inhibitors affect DNA methylation through their regulation on DNMT3B , a methyltransferase responsible for de novo DNA methylation . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
OBJECTIVE : DNA methyltransferase ( DNMT ) 1 , DNMT3b , or both , facilitate malignant transformation through chromatin remodeling mechanisms . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^ 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Cancer linked satellite DNA hypomethylation was independent of RNA levels for all DNMT3B isoforms , despite the ICF syndrome linked DNMT3B deficiency causing juxtacentromeric satellite DNA hypomethylation . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 ) . ^^^ ICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes ( DNMT3B ) . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
In this study , we have cloned human DNMT3A and DNMT3B that encode full length DNMT3A and DNMT3B proteins with 98 % and 94 % amino acid sequence identity to their murine homologues . ^^^ The DNMT3A and DNMT3B show high homology in the carboxy terminal catalytic domain and contain a conserved cysteine rich region , which shares homology with the 10 linked ATRX gene of the SNF2 / SWI family . ^^^ We have mapped human DNMT3A and DNMT3B to chromosomes 2p23 and 20q11 . 2 respectively , and determined the DNMT3B genomic structure . ^^^ We further show that DNMT3A expression is ubiquitous and can be readily detected in most adult tissues , whereas DNMT3B is expressed at very low levels in most tissues except testis , thyroid and bone marrow . ^^^ Significantly , both DNMT3A and DNMT3B expression is elevated in several tumor cell lines to levels comparable to DNMT 1 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
In vivo activity of murine de novo methyltransferases , Dnmt3a and Dnmt3b . ^^^ The putative de novo methyltransferases , Dnmt3a and Dnmt3b , were reported to have weak methyltransferase activity in methylating the 3 ' long terminal repeat of Moloney murine leukemia virus in vitro . ^^^ 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 . ^^^ It is also noteworthy that both Dnmt3a and Dnmt3b proteins coat the metaphase chromosomes while displaying a more uniform pattern in the nucleus . ^^^ This is the first evidence that Dnmt3a and Dnmt3b have de novo methyltransferase function in vivo and the first indication that the Dnmt3a and Dnmt3b proteins may have preferred target sites . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The encoded protein of 387 amino acids has a cysteine rich region containing a novel type zinc finger domain that is conserved in DNMT3A and DNMT3B but also in ATRX , a member of the SNF 2 protein family . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
We find that a DNA binding protein can protect sites on the episome as well as in the genome from the de novo methylation activity of Dnmt3a . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse : the enzyme modifies DNA in a non processive manner and also methylates non CpG [ correction of non CpA ] sites . ^^^ 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Gene silencing by promoter methylation requires Dnmt 1 , suggesting that the expression of Dnmt3a and Dnmt3b alone in ES cells is insufficient to achieve effective gene silencing . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The recently discovered de novo methyltransferases DNMT3a and DNMT3b have been shown to be critical to embryonic development . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^ In contrast , both Dnmt 1 and Dnmt3a and / or Dnmt3b were required for methylation of a select class of sequences which included abundant murine LINE 1 promoters . ^^^ We conclude that ongoing de novo methylation by Dnmt3a and / or Dnmt3b compensates for inefficient maintenance methylation by Dnmt 1 of these endogenous repetitive sequences . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Preferential methylation of unmethylated DNA by Mammalian de novo DNA methyltransferase Dnmt3a . ^^^ We report here that Dnmt3a is a true de novo methyltransferase that prefers unmethylated DNA substrates more than 3 fold to hemimethylated DNA . ^^^ Furthermore , Dnmt3a binds DNA nonspecifically , regardless of the presence of CpG dinucleotides in the DNA substrate . ^^^ Kinetic analysis supports an Ordered Bi Bi mechanism for Dnmt3a , where DNA binds first , followed by S adenosyl l methionine . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The mRNA levels of the de novo methyltransferases DNMT3a and DNMT3b were 3 and 6 fold higher , respectively , in the tumor implicating transcriptional up regulation of these two genes in this tissue . ^^^ Immunohistochemical analysis showed exclusive localization of DNMT3a in the nuclei of both the liver and hepatoma , whereas DNMT3b was detected in the nuclei as well as the cytoplasm . ^^^ Immunoblot assay showed that the levels of DNMT 1 , DNMT3a , and DNMT3b proteins in the hepatoma were 5 , 10 , and 4 fold higher , respectively , than in the liver . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Our results suggest that cell division is required for de novo methylation of CpG islands and that DNMT3a may play a role in methylating CpG poor regions or repetitive DNA elements outside of the S phase of the cell cycle . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Here , we show that Dnmt3L , like Dnmt3a and Dnmt3b , interacts both in vitro and in vivo with the histone deacetylase HDAC 1 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Dnmt3L , an isoform of Dnmt3a and Dnmt3b , but lacking enzymatic activity , interacts with Dnmt2a and Dnmt3b and is required for spermatogenesis . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Dnmt3a and Dnmt 1 functionally cooperate during de novo methylation of DNA . ^^^ Dnmt3a is a de novo DNA methyltransferase that modifies unmethylated 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 . ^^^ We conclude that after initiation of de novo methylation of DNA by Dnmt3a , Dnmt 1 becomes activated by the pre existing methyl groups and further methylates the DNA . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The DNA methyltransferase like protein DNMT3L stimulates de novo methylation by Dnmt3a . ^^^ The implications of these findings for the function of DNMT3L and Dnmt3a in DNA methylation and genomic imprinting are discussed . . ^^^ In an attempt to define its function , we coexpressed DNMT3L with each of the two known de novo methyltransferases , Dnmt3a and DNMT3B , in human cells and monitored de novo methylation by using replicating minichromosomes carrying various ICs as targets . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
In addition , expression of the presumed de novo methyltransferases DNMT3A and DNMT3B mRNAs was investigated . ^^^ DNMT3B overexpression was observed in about half of all high stage TCC ( DNMT3B vs . tumor stage , chi ( 2 ) : p = 0 . 03 ) , whereas overexpression of DNMT3A was rarer and less pronounced . ^^^ Expression of DNMT3A and DNMT3B in most RCC lines was higher than in TCC lines . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Finally , we demonstrate how this approach can yield insights into the role of DNA methylation during ES cell differentiation by studying the function of two genes : DNMT3A , involved in the de novo methylation of cytosine bases , and MBD2b , a methyl dependent co repressor and putative cytosine demethylase . . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Catalytic mechanism of DNA ( cytosine C 5 ) methyltransferases revisited : covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme . ^^^ Co transfections of reporter plasmids and plasmids encoding the catalytic domain of the murine Dnmt3a DNA methyltransferase lead to inhibition of reporter gene expression . ^^^ Whereas wild type Dnmt3a and the ENV variants form covalent complexes with 5 fluorocytidine modified DNA , the PCN variant does not . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Modification of de novo DNA methyltransferase 3a ( Dnmt3a ) by SUMO 1 modulates its interaction with histone deacetylases ( HDACs ) and its capacity to repress transcription . ^^^ The de novo DNA methyltransferase Dnmt3a is one of three mammalian DNA methyltransferases that has been shown to play crucial roles in embryonic development , genomic imprinting and transcriptional silencing . ^^^ Functionally , sumoylation of Dnmt3a disrupts its ability to interact with histone deacetylases ( HDAC1 / 2 ) , but not with another interaction partner , Dnmt3b . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
However , it is unknown whether differential de novo methylation at the Xist promoter , which is mediated by Dnmt3a and / or Dnmt3b , is a cause or a consequence of monoallelic expression of Xist . ^^^ We show that Xist expression is appropriately regulated in the absence of Dnmt3a and Dnmt3b and that a single 10 chromosome undergoes proper inactivation in mutant females . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
In addition , we show that methylation acquisition was probably related to oocyte diameter and coincided with the accumulation of Dnmt3a , Dnmt3b and Dnmt3L transcripts . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Dimethyl sulfoxide stimulates the catalytic activity of de novo DNA methyltransferase 3a ( Dnmt3a ) in vitro . ^^^ Mammalian DNA methyltransferase Dnmt3a is required for de novo methylation of CpG dinucleotides in genomic DNA . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Here we show that retrovirus is silent or variegated in mouse embryonic stem ( ES ) cells that are de novo methyltransferase ( dnmt3a and dnmt3b ) null . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Analysis using Dnmt deficient embryonic stem cell lines revealed that Dnmt 1 , Dnmt3a , and Dnmt3b are each partially responsible for maintenance of methylation of Dnmt1o T DMR . ^^^ In particular , there are compensatory and cooperative roles between Dnmt3a and Dnmt3b . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Expression of DNMT 1 , DNMT3a and DNMT3b mRNA was detected in 33 . 3 , 59 . 3 , and 55 . 6 % of HCCs and 40 . 7 , 22 . 2 , and 0 % of non neoplastic liver tissues , respectively . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^ In contrast , the prokaryotic SssI DNA methyltransferase and the catalytic domain of Dnmt3a are strongly inhibited by nucleosomes . ^^^ Variations of the DNA sequence or the histone tails did not significantly influence the methylation activity of Dnmt3a . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
It was found that trans repression by Dnmt3a does not require the methyltransferase activity implying that transcriptional repression does not involve promoter silencing through DNA methylation by Dnmt3a . ^^^ Finally , the activity of Dnmt3a in vivo was demonstrated when this enzyme was overexpressed in a breast cell line in which Dnmt3a repressed p 21 upregulation following DNA damage . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
CGH also revealed unique net chromosomal alterations in LNCaP r compared to LNCaP FGC , including gain of 2p13 23 , 2q21 32 , and 13q and loss of 6p22 pter . cDNA microarray analysis identified several genes involved in DNA methylation , such as DNMT 2 , DNMT3a , and methyl CpG binding domain protein 2 and 4 that were higher expressed in LNCaP r . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 / ] ) . ^^^ Non CpG methylation was > 250 fold reduced compared with wild type ES cells , consistent with a role for Dnmt3a and / or Dnmt3b in CpA and CpT methylation . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Mammals have three Dnmt 3 genes ; Dnmt3a , Dnmt3b , and Dnmt3L , two of which encode active enzymes and one of which produces an inactive but necessary cofactor . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
DNMT3b is restricted to mitotic olfactory progenitors , whereas DNMT3a is expressed only in post mitotic immature neurons prior to ORN terminal maturation , coincident with histone deacetylase 2 ( HDAC 2 ) , a key downstream effector of methylation dependent chromatin condensation . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
The mammalian DNMTs are DNMT 1 , DNMT3A and DNMT3B , which together with accessory proteins , like DNMT3L , are responsible for methylation pattern acquisition during gametogenesis , embryogenesis and somatic tissue development . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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 . ^^^ Lsh affects Dnmt3a as well as Dnmt3b directed methylation suggesting that Lsh can cooperate with both enzymatic activities . ^^^ Finally , we demonstrate that Lsh associates with Dnmt3a or Dnmt3b but not with Dnmt 1 in embryonic cells . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Recent data in mice indicate that Dnmt3a , an enzyme with de novo DNA methyltransferase activity , and the related protein Dnmt3L are required for methylation of imprinted loci in germ cells . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Expression of DNMT3A transcripts and nucleolar localization of DNMT3A protein in human testicular and fibroblast cells suggest a role for de novo DNA methylation in nucleolar inactivation . ^^^ It is associated with high expression of different transcripts of the DNA methyltransferase 3A ( DNMT3A ) gene that encode two isoforms with de novo methyltransferase activity and one without catalytic activity . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Mutational analysis of the catalytic domain of the murine Dnmt3a DNA ( cytosine C 5 ) methyltransferase . ^^^ On the basis of amino acid sequence alignments and structural data of related enzymes , we have performed a mutational analysis of 14 amino acid residues in the catalytic domain of the murine Dnmt3a DNA ( cytosine C 5 ) methyltransferase . ^^^ R130A displayed a strong reduction in catalytic activity and a complete change in flanking sequence preferences , indicating that Arg 130 has an important role in the DNA interaction of Dnmt3a . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
However , expression of the de novo methyltransferases Dnmt3a and Dnmt3b increased with aging in stimulated T cells from control mice . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
In mouse , one of the two de novo DNA methyltransferases , Dnmt3a , and a related protein , Dnmt3L have been shown to be essential for imprint establishment in the parental germline . ^^^ We cloned cDNAs for chicken DNMT3A and DNMT3B , whose putative protein products shared 81 . 5 % and 48 . 6 % amino acid sequence identity with their mouse orthologues . ^^^ Using computer assisted database searches , we also identified DNMT3A and DNMT3B orthologues in fish ( fugu and zebrafish ) and marsupials ( opossum ) . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^ Similarly , the Dnmt3a mRNA level was elevated in rats fed the FMD diet ( P < 0 . 001 ) , whereas the Dnmt3b level ( mRNA and protein ) was not affected by diet or age . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Significant regulations could be analyzed for 5 genes ( expression > 2 or < 0 . 5 fold ) : IL15RA ( Interleukin 15 receptor , alpha chain ) , EPS15R ( Epidermal growth factor receptor pathway substrate 15 like 1 ) , DNMT3A ( Hypothetical protein MGC 16121 ) , DNMT3A ( DNA ( cytosine 5 ) methyltransferase 3 alpha ) , and one gene with no match to known genes , DKFZP586J1624 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Here we show that during TH 2 polarization , the DNA methyltransferase Dnmt3a is recruited to the IFN gamma promoter and correspondingly the promoter undergoes progressive de novo methylation . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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 . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
We further determined that methylation in these CpG islands , which is probably triggered by de novo DNA methyltransferase Dnmt3a , is abnormally higher in hESC NPCs than in primary NPCs and astrocytes . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 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: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi ' s sarcoma associated herpesvirus LANA . ^^^ Further , LANA associated with repressed cellular promoters , recruited Dnmt3a to DNA , and facilitated de novo promoter methylation of a down regulated gene , cadherin 13 ( H cadherin ) . ^^^
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
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Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA
Interacting proteins: Q9Y6K1 and Q9UBC3 Pubmed SVM Score :0.0
NA