Affinage

DNMT3B

DNA (cytosine-5)-methyltransferase 3B · UniProt Q9UBC3

Length
853 aa
Mass
95.8 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNMT3B is a de novo DNA methyltransferase that establishes both CpG and non-CpG (CpA, CpT) methylation patterns at pericentromeric satellite repeats, gene bodies, active enhancers, and placental regulatory elements during mammalian development (PMID:10555141, PMID:27476967, PMID:36690623, PMID:12869530). Its catalytic domain operates through a non-cooperative, processive mechanism with substrate selectivity governed by a catalytic-loop hydrogen bond and key residues (notably K777) that sense flanking-sequence context, as revealed by crystal structure determination and systematic mutagenesis (PMID:32620778, PMID:33105482, PMID:27768276). Catalytically inactive DNMT3B isoforms (e.g., DNMT3B3) function as accessory factors that stimulate de novo methylation by active DNMT3 enzymes—structurally, DNMT3B3 binds the nucleosome acidic patch to orient catalytically active subunits toward linker DNA—and a catalytically dead knock-in rescues most methylation defects and embryonic lethality of Dnmt3b-null mice, demonstrating a major methylation-independent scaffolding and transcriptional repressor role (PMID:32968275, PMID:31558711, PMID:21378119). Loss-of-function mutations in DNMT3B cause ICF syndrome (immunodeficiency, centromeric instability, facial anomalies), characterized by pericentromeric satellite hypomethylation (PMID:10588719).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing that DNMT3B is a bona fide de novo methyltransferase essential for development resolved the identity of the enzyme responsible for establishing—rather than maintaining—CpG methylation at centromeric repeats.

    Evidence Gene targeting in mouse ES cells and embryos with bisulfite sequencing of satellite repeats

    PMID:10555141

    Open questions at the time
    • Locus-specific targeting mechanism unknown
    • Relationship to DNMT3A activity at overlapping targets unresolved
  2. 1999 High

    Linking DNMT3B catalytic-domain mutations to ICF syndrome established the first human disease caused by defective de novo methylation and pinpointed pericentromeric repeats as the critical substrate.

    Evidence Mutation analysis of ICF patients and somatic cell fusion complementation

    PMID:10588719

    Open questions at the time
    • Why pericentromeric repeats are selectively sensitive was unclear
    • Contribution of non-catalytic DNMT3B functions to ICF pathology not addressed
  3. 2001 High

    Demonstrating that DNMT3B represses transcription independently of its methyltransferase activity revealed a dual function—catalytic and structural/repressive—broadening its role beyond DNA methylation.

    Evidence Transcriptional repression assays and immunofluorescence in wild-type and Dnmt1-null ES cells

    PMID:11427539

    Open questions at the time
    • Identity of co-repressor complexes mediating methylation-independent repression unknown
    • Relative contribution of catalytic vs. non-catalytic functions in vivo untested
  4. 2002 High

    Showing that DNMT1 and DNMT3B cooperate to maintain >95% of genomic methylation in cancer cells clarified that de novo and maintenance methyltransferases are not strictly separable in somatic cells.

    Evidence Double genetic disruption in HCT116 colorectal cancer cells with quantitative methylation assays

    PMID:11932749

    Open questions at the time
    • Whether cooperation is direct or through sequential activity unresolved
    • Applicability beyond cancer cell lines not tested
  5. 2003 High

    Biochemical characterization revealed DNMT3B methylates CpA and CpT dinucleotides in addition to CpG, establishing it as a broader-specificity methyltransferase than DNMT3A.

    Evidence In vitro enzymatic assay with purified recombinant protein and oligonucleotide substrates

    PMID:12869530

    Open questions at the time
    • Physiological relevance of non-CpG methylation by DNMT3B not yet demonstrated in vivo
  6. 2005 High

    Reconstitution of DNMT3L-DNMT3B interaction showed DNMT3L acts as a substrate exchange factor that opens the active site, explaining how an enzymatically dead paralog stimulates de novo methylation.

    Evidence In vitro kinetics measuring Km changes for DNA and AdoMet upon DNMT3L addition, domain deletion mapping

    PMID:15105426 PMID:15671018

    Open questions at the time
    • Whether DNMT3L stimulation occurs at all genomic targets or is locus-specific unknown
    • Structural basis of conformational change not determined
  7. 2007 High

    In vivo overexpression of DNMT3B1 in a tumor model demonstrated it can drive gene-specific de novo methylation and silencing of tumor suppressors (Sfrp genes), directly linking DNMT3B gain-of-function to tumorigenesis.

    Evidence Transgenic DNMT3B1 overexpression in ApcMin/+ mice with bisulfite sequencing and expression analysis

    PMID:18056424

    Open questions at the time
    • Mechanism of locus-specific recruitment to Sfrp promoters not identified
    • Whether DNMT3B acts alone or with co-factors in tumor context unclear
  8. 2008 High

    Discovery that miR-148 targets DNMT3B1 through a coding-sequence site (not 3′UTR) established an unusual post-transcriptional regulatory mechanism and explained isoform-specific regulation.

    Evidence miRNA overexpression, site-directed mutagenesis of the CDS target, and reporter assays

    PMID:18367714

    Open questions at the time
    • Physiological contexts where miR-148 regulation is rate-limiting not defined
  9. 2016 High

    Genome-wide studies established that DNMT3B is recruited to active enhancers via H3K36me3 recognition through its PWWP domain, and that catalytically inactive isoforms function as DNMT3L-like accessory factors promoting gene-body methylation in somatic cells.

    Evidence ChIP-seq and genome-wide methylation profiling in epidermal stem cells; exogenous isoform expression with methylation analysis

    PMID:27121154 PMID:27476967

    Open questions at the time
    • Whether PWWP-H3K36me3 interaction is sufficient for recruitment or requires additional factors
    • Quantitative contribution of inactive isoforms vs. DNMT3L in different tissues unknown
  10. 2016 High

    Kinetic analysis showed DNMT3B catalyzes methylation by a non-cooperative processive mechanism, fundamentally distinguishing it from the cooperative mechanism of DNMT3A and explaining their different genomic methylation patterns.

    Evidence In vitro enzymatic assay with conditions discriminating cooperativity from processivity, plus R829H mutagenesis

    PMID:27768276

    Open questions at the time
    • How processivity is regulated on chromatin substrates unknown
    • Structural basis for non-cooperative behavior not resolved
  11. 2017 High

    In vivo demonstration that DNMT3B preferentially deposits non-CpG methylation at REST target genes in developing hearts connected its broader substrate specificity to a specific developmental gene-regulatory circuit.

    Evidence Mouse genetic model with bisulfite sequencing and ChIP for REST occupancy

    PMID:27956497

    Open questions at the time
    • Whether DNMT3B-dependent non-CpG methylation operates in tissues beyond heart unknown
    • Direct vs. indirect effect on REST binding not fully separated
  12. 2019 High

    A catalytically dead Dnmt3b knock-in rescued most methylation defects and embryonic lethality, proving that the majority of DNMT3B's developmental function is scaffolding/accessory rather than catalytic, and identifying Wnt9b as a direct transcriptional target.

    Evidence Catalytic-mutant knock-in mice, whole-genome bisulfite sequencing, ChIP, expression analysis

    PMID:31558711

    Open questions at the time
    • Mechanism by which catalytically dead DNMT3B restores methylation (presumably via DNMT3A stimulation) not directly shown
    • Full set of transcriptional targets of DNMT3B's repressor function undefined
  13. 2020 High

    Crystal structure of DNMT3B catalytic domain and cryo-EM of the DNMT3A2/DNMT3B3/nucleosome complex revealed the molecular basis for flanking-sequence selectivity (K777 as +1 base sensor, catalytic-loop hydrogen bond lowering CpG specificity) and how DNMT3B3 engages the nucleosome acidic patch to orient active enzymes toward linker DNA.

    Evidence X-ray crystallography, cryo-EM, systematic mutagenesis, in vitro methylation of randomized substrate pools

    PMID:32620778 PMID:32968275 PMID:33105482

    Open questions at the time
    • Structure of full-length DNMT3B on nucleosome not available
    • How DNA repositioning occurs to allow methylation of nucleosomal CpGs unresolved
  14. 2020 High

    Genome-wide knockout comparisons separated DNMT3A and DNMT3B target loci, showing DNMT3B dominates X-chromosome methylation while DNMT3A covers Polycomb-target developmental genes, and that DNMT3B3 preferentially stimulates DNMT3B2 over DNMT3A.

    Evidence Conditional knockouts in MEFs with whole-genome bisulfite sequencing; triple-KO mESC rescue with stoichiometry measurements

    PMID:32581223 PMID:33004415

    Open questions at the time
    • Molecular basis for DNMT3B3's preference for stimulating DNMT3B2 vs. DNMT3A unknown
    • Whether X-chromosome preference reflects recruitment or intrinsic substrate preference unclear
  15. 2023 High

    Conditional rescue showed DNMT3B's essential developmental role is primarily placental, where it silences germline genes in trophoblast; embryonic deletion alone is compatible with survival if placental DNMT3B is intact.

    Evidence Sox2-Cre conditional knockout with whole-genome bisulfite sequencing and transcriptomics

    PMID:36690623

    Open questions at the time
    • Identity of germline gene targets requiring DNMT3B in trophoblast not fully catalogued
    • Whether placental DNMT3B acts catalytically or as an accessory factor not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of full-length DNMT3B on chromatin, the mechanism by which catalytically dead DNMT3B stimulates DNMT3A at specific loci in vivo, and the relative contributions of catalytic vs. scaffolding functions in different developmental and disease contexts.
  • No full-length DNMT3B structure on nucleosomal substrate
  • In vivo mechanism of catalytically dead DNMT3B-mediated methylation rescue not reconstituted
  • Relative contribution of catalytic vs. accessory function in ICF syndrome pathology unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0016740 transferase activity 4 GO:0003677 DNA binding 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2
Partners
CUL4ADNMT1DNMT3ADNMT3LHOXB3NEDD8RBM10
Complex memberships
DNMT3A-DNMT3B3 heterotetramerDNMT3A2-DNMT3B3-nucleosome ternary complexDNMT3B-DNMT3L complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 DNMT3B functions as a de novo DNA methyltransferase essential for mouse development; genetic knockout blocks de novo methylation in ES cells and early embryos but does not affect maintenance of imprinted methylation patterns. DNMT3B is specifically required for methylation of centromeric minor satellite repeats. Gene targeting/knockout in mouse ES cells and embryos, bisulfite sequencing Cell High 10555141
1999 Missense mutations in the catalytic domain of DNMT3B cause ICF syndrome (immunodeficiency, centromeric instability, facial anomalies), with hypomethylation of pericentromeric satellite repeats; somatic cell fusion to CHO cells complements the hypomethylation defect, indicating conserved de novo methylation function. Mutation analysis of ICF patients, somatic cell fusion complementation assay Proceedings of the National Academy of Sciences of the United States of America High 10588719
2001 DNMT3B represses transcription in a methylation-independent manner, primarily through a plant homeodomain (PHD)-like motif shared with ATRX but absent in DNMT1. In murine embryonic stem cells, DNMT3B co-localizes with DNMT3A to pericentromeric heterochromatin, and this localization is independent of pre-existing methylation. Transcriptional repression assay, immunofluorescence co-localization, Dnmt1-null ES cell analysis The Journal of biological chemistry High 11427539
2002 DNMT1 and DNMT3B cooperatively maintain DNA methylation and gene silencing in human cancer cells; genetic disruption of both enzymes nearly eliminates methyltransferase activity and reduces genomic DNA methylation by >95%, causing demethylation of repeated sequences, loss of IGF2 imprinting, and reactivation of the p16INK4a tumor suppressor. Genetic disruption (gene targeting) of DNMT1 and DNMT3B in colorectal cancer cells, methylation assays, gene expression analysis Nature High 11932749
2003 Recombinant DNMT3B methylates CpA and CpT (but not CpC) in addition to CpG, showing broader non-CpG methylation activity than DNMT3A, which only methylates CpA among non-CpG sites. DNMT3B is inhibited by sodium at physiological potassium concentrations, unlike DNMT3A. In vitro enzymatic assay with purified recombinant protein, oligonucleotide substrate analysis Journal of biochemistry High 12869530
2004 DNMT3L directly interacts with DNMT3B and stimulates its DNA methylation activity 1.5-3-fold in vitro; DNMT3L binds DNMT3B but not DNA, indicating the stimulatory effect is via direct enzyme activation rather than DNA targeting. In vitro methylation assay, direct binding assay with purified proteins, C-terminal domain deletion analysis The Journal of biological chemistry High 15105426
2005 DNMT3L stimulates DNMT3B catalytic activity by directly binding to the DNMT3B catalytic domain via its own C-terminal domain, inducing a conformational change that opens the active site and promotes DNA and AdoMet binding; DNMT3L acts as a substrate exchange factor and dissociates from DNMT3B after DNA binding. In vitro enzymatic assay, direct binding assay, kinetics (Km measurements for DNA and AdoMet), domain deletion analysis The Journal of biological chemistry High 15671018
2007 DNMT3B1 overexpression in Apc Min/+ mice promotes colon tumorigenesis by gene-specific de novo methylation and transcriptional silencing of tumor suppressor genes (Sfrp2, Sfrp4, Sfrp5) and induces loss of Igf2 imprinting; DNMT3B1 but not DNMT3A1 efficiently methylates the same gene targets in tumors and normal tissue. Transgenic mouse overexpression in Apc Min/+ background, bisulfite sequencing, gene expression analysis Genes & development High 18056424
2008 miR-148 represses DNMT3B1 expression through a target site within its protein coding sequence (not 3'UTR); mutating the coding-sequence target site abolishes miR-148 regulation, and DNMT3B3 (which lacks the target site) is resistant to miR-148. miRNA overexpression/shRNA knockdown, site-directed mutagenesis of target site, reporter assay RNA (New York, N.Y.) High 18367714
2009 HOXB3 binds the DNMT3B gene and increases its expression; DNMT3B is then recruited to the RASSF1A promoter through interactions with Polycomb repressor complex 2 and MYC, causing hypermethylation and transcriptional silencing of RASSF1A. shRNA screen, ChIP, promoter reporter assay, siRNA knockdown, xenograft experiments Molecular cell High 19854132
2010 DNMT3B interacts directly with NEDD8 in vitro and preferentially co-immunoprecipitates the NEDDylated form of CUL4A in vivo; NEDD8 enhances DNMT3B-dependent DNA methylation, and DNMT3B recruits CUL4A and NEDD8 to chromatin. Co-immunoprecipitation, in vitro binding, ChIP, methylation assay, Dnmt3b-null cell comparison The Journal of biological chemistry Medium 20847044
2011 DNMT3B splice variants interact with each other and with DNMT3A and DNMT3L; the PWWP domain (not only the C-terminal catalytic domain) contributes to DNA binding and nuclear localization. Catalytically inactive DNMT3B isoforms can modulate the activity of DNMT3A-DNMT3L complexes. DNMT3B self-interactions regulate its methylation activity. In vitro methylation assay, DNA binding assay, protein-protein interaction assays, cellular localization imaging Nucleic acids research High 21378119
2013 Catalytically inactive DNMT3B3 stimulates de novo methylation by DNMT3A but counteracts DNMT3L stimulation; DNMT3B4 inhibits de novo methylation by active DNMT3 enzymes by reducing DNA binding affinity. Both isoforms drive distinct chromatin compaction patterns and H3K9me3 deposition independent of methylation activity. In vitro methylation assay, protein complex formation, immunocytochemistry, H3K9me3 ChIP PloS one Medium 23894490
2016 Catalytically inactive DNMT3B isoforms stimulate gene body methylation and facilitate re-methylation after demethylation treatment independently of their own catalytic activity, acting similarly to the accessory protein DNMT3L by recruiting DNMT3A in somatic cells. Exogenous isoform expression, methylation analysis, DNMT3L complementation comparison Nature communications Medium 27121154
2016 In human epidermal stem cells, DNMT3B binds to active enhancers in an H3K36me3-dependent manner and promotes DNA methylation along enhancer bodies; DNMT3B depletion inactivates target enhancers and disrupts epidermal stem cell function. ChIP-seq, genome-wide methylation profiling, siRNA knockdown, stem cell functional assays Cell stem cell High 27476967
2016 DNMT3B-C catalytic domain methylates DNA by a non-cooperative, processive mechanism, in contrast to DNMT3A-C which is cooperative. The analogous R829H mutation in DNMT3B (homologue of AML-associated R882H in DNMT3A) does not disrupt its activity or processivity, indicating dimer interface interactions play a limited role in DNMT3B regulation. In vitro enzymatic assay under conditions distinguishing cooperativity from processivity, site-directed mutagenesis, kinetic analysis Biochemistry High 27768276
2017 DNMT3B preferentially mediates non-CpG methylation of REST (RE1 silencing transcription factor) target gene sequences in developing mouse hearts; reduced DNMT3B expression decreases non-CpG methylation of RE1 sequences, reduces REST occupancy, and releases transcriptional suppression of adult cardiac genes. Mouse genetic model, bisulfite sequencing, ChIP, in vitro methylation assay, cardiac gene expression analysis Nucleic acids research High 27956497
2019 Catalytically inactive Dnmt3b can rescue the majority of methylation and gene expression changes in Dnmt3b knockout embryos, enabling survival through embryogenesis; Dnmt3b directly represses Wnt9b as a transcriptional repressor, and aberrant Wnt9b upregulation contributes to embryonic lethality in Dnmt3b knockouts. Knock-in of catalytically inactive Dnmt3b in mice, whole genome bisulfite sequencing, gene expression analysis, ChIP Nature communications High 31558711
2020 DNMT3B has lower CpG specificity than DNMT3A due to a hydrogen bond in its catalytic loop; the interplay between the target recognition domain and homodimeric interface fine-tunes substrate selection, with Lysine 777 acting as a unique sensor of the +1 flanking base. Crystal structure and mutagenesis of DNMT3B revealed the multi-layered substrate-recognition mechanism. Crystal structure determination, in vitro enzymatic assay, mutagenesis, cellular methylation profiling Nature communications High 32620778
2020 Cryo-EM structure of DNMT3A2/DNMT3B3/nucleosome ternary complex reveals that the catalytic-like domain of the accessory DNMT3B3 binds the acidic patch of the nucleosome core, orienting DNMT3A2 binding to linker DNA; steric constraints suggest nucleosomal DNA must be repositioned for de novo methylation. Cryo-EM structure determination of ternary complex Nature High 32968275
2020 DNMT3B has complex flanking sequence readout mechanisms; T775 has an essential dynamic role in the catalytic mechanism, and six residues (N652, N656, N658, K777, N779, R823) in the DNA-binding interface equalize CpG methylation rates in diverse flanking contexts by forming compensatory interactions; non-CpG flanking preferences of DNMT3B correlate with cellular non-CpG methylation patterns. In vitro methylation of randomized substrate pools, mutagenesis, kinetic analysis Nucleic acids research High 33105482
2020 Inactive Dnmt3b3 isoform preferentially stimulates Dnmt3b-mediated de novo methylation over Dnmt3a, forming a 2:2 complex with Dnmt3a2 similar to Dnmt3L; in triple-knockout mESC rescue experiments, Dnmt3b3 preferentially supports Dnmt3b2-mediated genomic remethylation. In vitro methylation assay, SEC-MALS complex stoichiometry, triple-knockout mESC rescue experiments Genes & development High 33004415
2020 DNMT3A and DNMT3B establish de novo methylation at distinct genomic loci during mammalian development; DNMT3B has a dominant role on the X chromosome, while DNMT3A is exclusively required at TSS regions and gene bodies of Polycomb group target developmental genes. Conditional Dnmt3a/Dnmt3b knockout MEFs derived from 2i-ES cells, whole-genome bisulfite sequencing Nature communications High 32581223
2023 DNMT3B is principally required for de novo DNA methylation in placental trophoblast lineages to silence germline genes; Sox2-Cre deletion of Dnmt3b only in the embryo (leaving placental expression intact) rescues placental defects and embryonic lethality of Dnmt3b null mice, demonstrating that DNMT3B's essential developmental role operates primarily through placental regulation. Conditional knockout using Sox2-Cre, whole-genome bisulfite sequencing, transcriptomics Nature communications High 36690623
2017 DNMT3B directly represses Wnt9b as a transcriptional repressor during mouse embryogenesis; Rbm10-mediated alternative splicing of Dnmt3b controls the ratio of catalytically active (Dnmt3b2) to inactive (Dnmt3b3) isoforms, thereby modulating NF-κB-responsive promoter methylation and inflammatory gene expression. Rbm10 knockout mouse, RT-PCR isoform analysis, NF-κB target gene expression, promoter methylation assay International immunology Medium 29309623
2014 FOXO3a transcriptionally represses DNMT3B by binding to two elements in the DNMT3B promoter; MDM2-mediated degradation of FOXO3a relieves this repression, leading to DNMT3B overexpression in lung cancer. Luciferase reporter assay, ChIP, siRNA knockdown, chromatin structure analysis, xenograft model Journal of thoracic oncology Medium 25122426
2017 Loss of Dnmt3b in chondrocytes (Agc1CreERT2;Dnmt3bf/f) causes impaired chondrocyte maturation, delayed angiogenesis, and fracture repair defects; DNMT3B promotes CXCL12 and osteopontin expression by methylating the Cxcl12 promoter in chondrocytes, and CXCL12/OPN supplementation rescues tube formation defects. Conditional knockout mouse, fracture healing model, bisulfite sequencing, protein array, in vitro angiogenesis assay Journal of bone and mineral research Medium 29024060
2016 ICF syndrome-associated DNMT3B dysfunction alters intragenic CpG methylation and impairs multiple aspects of transcriptional regulation including alternative TSS usage, antisense transcription, and exon splicing; DNMT3B interacts with RNA molecules to modulate sense-antisense regulatory circuits and alternative splicing. Transcriptomic and epigenomic profiling of ICF patient B-cell lines, ChIP-seq, RNA-seq Nucleic acids research Medium 28334849

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 4541 10555141
2002 DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 1011 11932749
1999 The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proceedings of the National Academy of Sciences of the United States of America 572 10588719
2008 miR-148 targets human DNMT3b protein coding region. RNA (New York, N.Y.) 435 18367714
2015 Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nature genetics 379 25822089
2001 Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. The Journal of biological chemistry 355 11427539
2004 DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. The Journal of biological chemistry 345 15105426
2014 Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem cells. Cell stem cell 278 25130491
2005 Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. The Journal of biological chemistry 226 15671018
2007 Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes & development 225 18056424
2016 Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis. Cell stem cell 172 27476967
2020 Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nature communications 146 32620778
2006 Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertility and sterility 145 17081533
2002 An essential role for DNA methyltransferase DNMT3B in cancer cell survival. The Journal of biological chemistry 132 12015329
2019 Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation. Molecular cancer 126 30979371
2006 Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. Journal of neural transmission (Vienna, Austria : 1996) 122 16463117
2007 Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins. Oncogene 121 17353906
2016 DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells. Nature communications 111 27121154
2005 De novo DNA methyltransferases Dnmt3a and Dnmt3b primarily mediate the cytotoxic effect of 5-aza-2'-deoxycytidine. Oncogene 108 15735669
2009 Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression. Molecular cell 105 19854132
2019 Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia. Biomarker insights 97 31105426
2011 Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas. Journal of neuro-oncology 97 21229291
2013 Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells. Molecular cancer 93 24001151
2005 DNMT3B mutations and DNA methylation defect define two types of ICF syndrome. Human mutation 93 15580563
2020 Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B. Nature 90 32968275
2009 DNMT1 and DNMT3B modulate distinct polycomb-mediated histone modifications in colon cancer. Cancer research 88 19723660
2019 miR-29c-3p regulates DNMT3B and LATS1 methylation to inhibit tumor progression in hepatocellular carcinoma. Cell death & disease 85 30718452
2002 Three novel DNMT3B mutations in Japanese patients with ICF syndrome. American journal of medical genetics 85 12239717
2016 DNA methylation by DNMT1 and DNMT3b methyltransferases is driven by the MUC1-C oncoprotein in human carcinoma cells. Oncogene 78 27212035
2015 miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1. Oncotarget 75 26497367
2008 Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus. Immunology 75 18194272
2023 Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B. Nature communications 68 36690623
2017 Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence. Molecular psychiatry 68 28972577
2015 Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis. Experimental and molecular pathology 68 25746661
2016 Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases. Advances in experimental medicine and biology 67 27826835
2020 Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development. Nature communications 65 32581223
2022 m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency. Clinical and translational medicine 62 35340126
2003 Distinct enzymatic properties of recombinant mouse DNA methyltransferases Dnmt3a and Dnmt3b. Journal of biochemistry 62 12869530
2016 Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study. Aging cell 59 27169697
2021 FOXC1 promotes HCC proliferation and metastasis by Upregulating DNMT3B to induce DNA Hypermethylation of CTH promoter. Journal of experimental & clinical cancer research : CR 58 33522955
2020 The inactive Dnmt3b3 isoform preferentially enhances Dnmt3b-mediated DNA methylation. Genes & development 57 33004415
2012 Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient. Epigenetics 56 22595875
2018 A novel miR-375-HOXB3-CDCA3/DNMT3B regulatory circuitry contributes to leukemogenesis in acute myeloid leukemia. BMC cancer 54 29439669
2016 DNMT1, DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis. EBioMedicine 54 27789275
2011 Modulation of Dnmt3b function in vitro by interactions with Dnmt3L, Dnmt3a and Dnmt3b splice variants. Nucleic acids research 54 21378119
2017 Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 53 28278502
2022 DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy. Frontiers in cell and developmental biology 52 35620052
2017 DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos. Journal of molecular histology 52 29027601
2011 Maintenance of DNA methylation: Dnmt3b joins the dance. Epigenetics 51 22048250
2022 DNMT3B-mediated FAM111B methylation promotes papillary thyroid tumor glycolysis, growth and metastasis. International journal of biological sciences 50 35864964
2007 Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner. Cancer research 49 18006804
2019 MicroRNA-29a Disrupts DNMT3b to Ameliorate Diet-Induced Non-Alcoholic Steatohepatitis in Mice. International journal of molecular sciences 48 30917489
2013 Inactive DNMT3B splice variants modulate de novo DNA methylation. PloS one 48 23894490
2002 The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents. Biochimica et biophysica acta 48 12359337
2013 DNMT1, DNMT3A and DNMT3B gene variants in relation to ovarian cancer risk in the Polish population. Molecular biology reports 47 23666104
2020 Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21. Molecular therapy oncolytics 44 32382655
2017 ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing. Nucleic acids research 44 28334849
2019 Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway. Journal of molecular and cellular cardiology 43 31733201
2008 Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos. Gene expression patterns : GEP 42 18814855
2021 TCF3 is epigenetically silenced by EZH2 and DNMT3B and functions as a tumor suppressor in endometrial cancer. Cell death and differentiation 40 34175897
2020 Induction of DNMT3B by PGE2 and IL6 at Distant Metastatic Sites Promotes Epigenetic Modification and Breast Cancer Colonization. Cancer research 39 32265226
2013 Dnmt3b is a haploinsufficient tumor suppressor gene in Myc-induced lymphomagenesis. Blood 39 23315164
2016 Increased DNA methylation of Dnmt3b targets impairs leukemogenesis. Blood 38 26729896
2014 DNMT3B overexpression by deregulation of FOXO3a-mediated transcription repression and MDM2 overexpression in lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 38 25122426
2011 DNMT3B gene amplification predicts resistance to DNA demethylating drugs. Genes, chromosomes & cancer 38 21484930
2016 miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine. Experimental cell research 35 27426728
2010 DNMT1 and DNMT3b silencing sensitizes human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8. Cancer science 35 20398055
2021 DNMT1 and DNMT3B regulate tumorigenicity of human prostate cancer cells by controlling RAD9 expression through targeted methylation. Carcinogenesis 34 32780107
2016 Loss of Dnmt3b accelerates MLL-AF9 leukemia progression. Leukemia 34 27133822
2017 Non-CpG methylation by DNMT3B facilitates REST binding and gene silencing in developing mouse hearts. Nucleic acids research 33 27956497
2016 Dnmt1, Dnmt3a and Dnmt3b cooperate in photoreceptor and outer plexiform layer development in the mammalian retina. Experimental eye research 33 27865785
2014 Global identification of genes targeted by DNMT3b for epigenetic silencing in lung cancer. Oncogene 33 24469050
2014 Significance of DNMT3b in oral cancer. PloS one 33 24625449
2012 Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma. Cancer research 33 22815530
2019 Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions. Nature communications 32 31558711
2018 Targets and genomic constraints of ectopic Dnmt3b expression. eLife 31 30468428
2017 Loss of Dnmt3b in Chondrocytes Leads to Delayed Endochondral Ossification and Fracture Repair. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 31 29024060
2017 Rbm10 regulates inflammation development via alternative splicing of Dnmt3b. International immunology 31 29309623
2022 MicroRNA-20a-5p inhibits the autophagy and cisplatin resistance in ovarian cancer via regulating DNMT3B-mediated DNA methylation of RBP1. Reproductive toxicology (Elmsford, N.Y.) 30 34990753
2023 Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance. Journal of translational medicine 29 37705098
2022 Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases. Advances in experimental medicine and biology 29 36350506
2022 piRNA-6426 increases DNMT3B-mediated SOAT1 methylation and improves heart failure. Aging 28 35354120
2021 HOTAIR suppresses PTEN via DNMT3b and confers drug resistance in acute myeloid leukemia. Hematology (Amsterdam, Netherlands) 28 33538241
2010 De novo DNA methyltransferase DNMT3b interacts with NEDD8-modified proteins. The Journal of biological chemistry 28 20847044
2021 Interaction between DNMT3B and MYH11 via hypermethylation regulates gastric cancer progression. BMC cancer 27 34380460
2015 Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma. Digestive diseases and sciences 27 26660680
2020 DNMT3B silencing suppresses migration and invasion by epigenetically promoting miR-34a in bladder cancer. Aging 25 33221743
2023 MiR-129-2-3p Inhibits Esophageal Carcinoma Cell Proliferation, Migration, and Invasion via Targeting DNMT3B. Current molecular pharmacology 24 35260066
2021 DNMT3A and DNMT3B Targeting as an Effective Radiosensitizing Strategy in Embryonal Rhabdomyosarcoma. Cells 24 34831178
2020 miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer. Bioscience reports 24 32065219
2019 MiR-29b suppresses proliferation and mobility by targeting SOX12 and DNMT3b in pancreatic cancer. Anti-cancer drugs 24 30601190
2016 A novel miR-203-DNMT3b-ABCG2 regulatory pathway predisposing colorectal cancer development. Molecular carcinogenesis 24 27253631
2004 Expression of Dnmt3b in mouse hematopoietic progenitor cells and spermatogonia at specific stages. Gene expression patterns : GEP 24 15533817
2020 Dnmt3a and Dnmt3b-Decommissioned Fetal Enhancers are Linked to Kidney Disease. Journal of the American Society of Nephrology : JASN 23 32127410
2020 Complex DNA sequence readout mechanisms of the DNMT3B DNA methyltransferase. Nucleic acids research 23 33105482
2018 Ablation of Dnmt3b in chondrocytes suppresses cell maturation during embryonic development. Journal of cellular biochemistry 23 29637597
2021 Pterostilbene leads to DNMT3B-mediated DNA methylation and silencing of OCT1-targeted oncogenes in breast cancer cells. The Journal of nutritional biochemistry 21 34242723
2020 The acute myeloid leukemia variant DNMT3A Arg882His is a DNMT3B-like enzyme. Nucleic acids research 21 32123902
2020 LINC00240 promotes gastric cancer cell proliferation, migration and EMT via the miR-124-3p / DNMT3B axis. Cell biochemistry and function 21 32526811
2016 Dnmt3b Methylates DNA by a Noncooperative Mechanism, and Its Activity Is Unaffected by Manipulations at the Predicted Dimer Interface. Biochemistry 21 27768276