Affinage

DNMT3B

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

Length
853 aa
Mass
95.8 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNMT3B is a de novo DNA methyltransferase that establishes cytosine methylation at centromeric satellite repeats, gene bodies, and active enhancers during embryonic and tissue development (PMID:10555141, PMID:27476967). Genetic ablation in mice blocks de novo methylation and is specifically required for methylation of centromeric minor satellite repeats (PMID:10555141), and missense and splice mutations in DNMT3B cause ICF syndrome, characterized by pericentromeric satellite hypomethylation (PMID:10588719). Structurally, DNMT3B operates by a non-cooperative (processive) catalytic mechanism distinct from DNMT3A, with a catalytic-loop hydrogen bond and a unique +1 flanking-base sensor (Lys777) that confer lower CpG specificity and characteristic flanking-sequence preferences (PMID:32620778, PMID:27768276). Its activity is allosterically gated by an autoinhibitory ADD-MTase interaction and by PWWP-dependent oligomerization, with chromatin reading through ADD-H3K4me0 and PWWP-H3K36me3 binding (PMID:37941146), and ICF mutations at the FF homo-oligomerization interface impair DNA binding and heterochromatin targeting (PMID:35869095). DNMT3B is stimulated by DNMT3L and by catalytically inactive isoforms such as DNMT3B3, which acts as a DNMT3L-like accessory factor that forms a 2:2 complex with DNMT3A2 and preferentially supports DNMT3B2 (PMID:15105426, PMID:33004415); the inactive DNMT3B3 domain docks onto the nucleosome acidic patch to orient the catalytic enzyme toward linker DNA (PMID:32968275). Beyond catalysis, DNMT3B functions as a non-catalytic accessory cofactor — catalytically dead DNMT3B rescues most methylation defects and embryonic lethality of Dnmt3b-null embryos — and as a direct transcriptional repressor of genes including Wnt9b (PMID:31558711). It cooperates with DNMT1 (but not DNMT3A) for maintenance methylation (PMID:38376465), and DNMT3B loss destabilizes centromeric R-loops, generating endonuclease-driven breaks and chromosomal instability (PMID:35688824). Its expression is post-transcriptionally controlled by miR-148, HuR, Rbm10-dependent splicing, and Akt-coupled protein stability (PMID:18367714, PMID:19270063, PMID:24001151, PMID:29309623).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 High

    Established DNMT3B as a developmentally essential de novo methyltransferase with locus specificity, resolving which DNMT initiates methylation at centromeric repeats and linking it to human disease.

    Evidence Knockout mice with bisulfite methylation analysis, plus ICF patient mutation screening with somatic cell fusion complementation

    PMID:10555141 PMID:10588719

    Open questions at the time
    • Did not define the catalytic mechanism or sequence preferences
    • Targeting determinants to centromeric satellite not established
  2. 2002 High

    Showed DNMT3B acts together with DNMT1 to maintain genomic methylation and silencing in human cells, distinguishing cooperative maintenance from de novo activity.

    Evidence Targeted gene disruption in colorectal cancer cells with methyltransferase assays, bisulfite sequencing, and imprinting/silencing readouts

    PMID:11932749

    Open questions at the time
    • Whether DNMT3A also cooperates with DNMT1 was not resolved here
    • Molecular basis of DNMT1-DNMT3B cooperation undefined
  3. 2004 High

    Identified DNMT3L as a direct protein partner that stimulates DNMT3B catalysis rather than its DNA targeting, framing accessory-factor regulation of activity.

    Evidence In vitro methyltransferase and binding assays with DNMT3L domain deletions

    PMID:15105426

    Open questions at the time
    • Structural basis of stimulation not defined
    • In vivo relevance of the 1.5-3 fold effect unclear
  4. 2007 High

    Demonstrated that DNMT3A and DNMT3B form a native complex and mutually stimulate activity independent of catalysis, foreshadowing non-catalytic regulatory roles.

    Evidence Native complex purification, reciprocal Co-IP, in vitro activity assays with catalytic mutants, and bisulfite sequencing of Oct4/Nanog promoters

    PMID:17938196

    Open questions at the time
    • Stoichiometry and structure of the complex not determined
    • Whether DNMT3A-DNMT3B cooperate in vivo for maintenance not addressed
  5. 2008 Medium

    Defined post-transcriptional control of DNMT3B by miR-148 acting on the coding region, with isoform-selective escape, explaining differential isoform regulation.

    Evidence miRNA overexpression/knockdown and site-directed mutagenesis of the target site with mRNA/protein quantification

    PMID:18367714

    Open questions at the time
    • Physiological contexts where miR-148 controls DNMT3B not mapped
    • Downstream methylation consequences not measured
  6. 2009 Medium

    Showed mRNA stability control of DNMT3B by HuR couples the enzyme to stress signaling, linking transcript half-life to global methylation.

    Evidence Endogenous HuR RNP-IP, biotinylated RNA pulldown, mRNA stability and global methylation assays with cisplatin treatment

    PMID:19270063

    Open questions at the time
    • Single lab; signaling pathway driving HuR dissociation incompletely defined
    • Locus-specific methylation effects not resolved
  7. 2010 Medium

    Connected DNMT3B to the NEDDylation/cullin machinery, identifying NEDDylated CUL4A as a partner that enhances DNMT3B-dependent methylation and chromatin recruitment.

    Evidence Co-IP, in vitro NEDD8 binding, ChIP at a repressed promoter, and Dnmt3b deletion in a cancer cell line

    PMID:20847044

    Open questions at the time
    • Functional role of CUL4A recruitment in normal development unclear
    • Whether NEDDylation regulates DNMT3B turnover not addressed
  8. 2012 Medium

    Reported an in vitro 5-hmC dehydroxymethylase activity for DNMT3A/3B dependent on their catalytic sites, raising a possible demethylation-related function.

    Evidence In vitro biochemical dehydroxymethylation assay with active-site mutagenesis

    PMID:22898819

    Open questions at the time
    • In vitro reconstitution not independently replicated in this corpus
    • Physiological significance in cells/embryos unestablished
  9. 2014 High

    Genetic epistasis in HSCs revealed synergy between Dnmt3a and Dnmt3b and that the predominant adult-HSC Dnmt3b isoform is catalytically inactive yet functionally consequential.

    Evidence Conditional single and combined KO mice, HSC transplantation, whole-genome bisulfite sequencing, pathway analysis

    PMID:25130491

    Open questions at the time
    • Mechanism of inactive-isoform contribution not biochemically defined here
    • How combined loss activates beta-catenin signaling unresolved
  10. 2016 High

    Distinguished DNMT3B's catalytic mechanism as non-cooperative/processive, unlike DNMT3A, and showed the dimer interface plays a limited regulatory role.

    Evidence In vitro methylation kinetics, R829H mutagenesis (analogous to DNMT3A R882H), and buffer acidification experiments

    PMID:27768276

    Open questions at the time
    • Structural basis of processivity not yet visualized
    • Whether processivity shapes genomic targeting unaddressed
  11. 2016 Medium

    Defined non-catalytic accessory roles of inactive DNMT3B isoforms in stimulating gene-body methylation and recruiting DNMT3A, extending the DNMT3L-like paradigm to somatic cells, and connected DNMT3B to enhancer methylation, REST-directed non-CpG methylation, and melanoma suppression via miR-196b/RICTOR/mTORC2.

    Evidence Re-methylation assays after 5-aza with catalytic-mutant isoforms; ChIP-seq/RRBS at enhancers in epidermal stem cells; Dnmt3b KO hearts with CpG/non-CpG bisulfite and REST ChIP; conditional KO melanoma model with target validation

    PMID:26923591 PMID:27121154 PMID:27476967 PMID:27956497

    Open questions at the time
    • Recruitment specificity of inactive isoforms across tissues not unified
    • Direct versus indirect transcriptional effects partly inferred
  12. 2017 Medium

    Established Rbm10-mediated alternative splicing as a controller of the active/inactive DNMT3B isoform ratio with consequences for NF-kB-responsive promoter methylation and inflammation.

    Evidence Rbm10 KO mice and cells, isoform RT-PCR, bisulfite sequencing of NF-kB targets, NF-kB ChIP, Dnmt3b2 overexpression

    PMID:29309623

    Open questions at the time
    • Generalizability beyond the inflammatory loci tested unclear
    • Single lab
  13. 2018 Medium

    Showed DNMT3B acts as a direct transcriptional repressor of Rbpjk to control Notch signaling during skeletal progenitor differentiation and fracture repair.

    Evidence Conditional KO mice (Prx1-Cre), ChIP-defined Rbpjk binding, luciferase reporters, differentiation assays, pharmacologic Rbpjk rescue

    PMID:32051335

    Open questions at the time
    • Whether repression requires catalysis at Rbpjk not separated
    • Cofactors mediating repression unidentified
  14. 2019 High

    Definitively established a catalysis-independent function: a catalytically dead Dnmt3b rescues most methylation, transcriptome changes, and embryonic lethality, and directly represses Wnt9b.

    Evidence Catalytically inactive Dnmt3b knock-in mice with genome-wide methylation and transcriptomics; Akt-DNMT3B interaction Co-IP defining stability control via mahanine

    PMID:24001151 PMID:31558711

    Open questions at the time
    • Molecular partners executing the accessory function not fully defined
    • How Akt regulates DNMT3B ubiquitination mechanistically unresolved
  15. 2020 High

    Structural and enzymological work explained DNMT3B's distinct CpG specificity and flanking-base sensing, and visualized accessory DNMT3B3 docking on the nucleosome acidic patch to position the active enzyme; rescue in triple-KO mESCs showed DNMT3B3 rivals DNMT3L and preferentially supports DNMT3B2.

    Evidence Crystal structures with enzymology and mutagenesis; randomized-flank in vitro methylation with interface-residue mutagenesis; cryo-EM of DNMT3A2-DNMT3B3-nucleosome; in vitro stoichiometry plus triple-KO mESC rescue and genome-wide methylation

    PMID:32620778 PMID:32968275 PMID:33004415 PMID:33105482

    Open questions at the time
    • How nucleosomal DNA is repositioned for methylation not directly observed
    • In vivo balance of homo- versus accessory complexes incompletely quantified
  16. 2022 High

    Cryo-EM of the DNMT3B homo-oligomer defined a distinct FF interface and showed ICF mutations there impair DNA binding and heterochromatin targeting; parallel work linked DNMT3B loss to centromeric R-loop instability.

    Evidence Cryo-EM homo-oligomer structure with DNA-binding and ChIP/methylation assays using ICF mutants; KO/ICF cells with DNA-damage ChIP-seq, R-loop imaging, and endonuclease inhibition

    PMID:35688824 PMID:35869095

    Open questions at the time
    • How the homo-oligomer interconverts with heterotetramers in cells unresolved
    • R-loop instability mechanism downstream of XPG/XPF cleavage not fully mapped
  17. 2023 High

    Defined the allosteric architecture of DNMT3B — ADD-mediated autoinhibition and PWWP-driven tetramer assembly coupled to substrate-site folding — and showed a placenta-specific requirement underlying embryonic lethality.

    Evidence Cryo-EM under multiple oligomerization states with biochemistry; Sox2-Cre embryo-restricted deletion versus global KO with whole-genome bisulfite, transcriptomics, and placental histology

    PMID:36690623 PMID:37941146

    Open questions at the time
    • How histone-mark binding switches activity in chromatin context not fully integrated
    • Trophoblast-specific targeting determinants undefined
  18. 2024 Medium

    Showed DNMT3B specifically (not DNMT3A) cooperates with DNMT1 for maintenance methylation, with demethylation reversibly remodeling heterochromatin and genome compartmentalization.

    Evidence Inducible DNMT1 degradation (dTAG), whole-genome bisulfite sequencing, Hi-C, lamina-associated domain analysis, live imaging

    PMID:38376465

    Open questions at the time
    • Direct physical basis of DNMT1-DNMT3B cooperation not shown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DNMT3B's oligomerization states, accessory-isoform complexes, and histone-mark reading are dynamically coordinated to select specific genomic loci in vivo remains unresolved.
  • No unified model linking chromatin context to oligomeric state in cells
  • Recruitment determinants at centromeres versus enhancers versus gene bodies not reconciled
  • In vivo significance of in vitro 5-hmC dehydroxymethylase activity unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-73894 DNA Repair 1
Partners
AKTCUL4ADNMT1DNMT3ADNMT3B3DNMT3LHURNEDD8
Complex memberships
DNMT3A-DNMT3B complexDNMT3A2-DNMT3B3-nucleosome ternary complexDNMT3B methyltransferase homo-oligomerDNMT3B-DNMT3L heterotetramer

Evidence

Reading pass · 29 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, and Dnmt3b is specifically required for methylation of centromeric minor satellite repeats. Gene targeting (knockout mice), bisulfite sequencing, methylation analysis of ES cells and embryos Cell High 10555141
1999 Missense mutations and a splice-site insertion in DNMT3B cause ICF syndrome, characterized by hypomethylation of pericentromeric satellite repeats on chromosomes 1, 9, and 16; somatic cell fusion complemented the hypomethylation defect, indicating DNMT3B promotes de novo methylation at these loci. Mutation screening of ICF patients, somatic cell fusion complementation assay, bisulfite methylation analysis Proceedings of the National Academy of Sciences of the United States of America High 10588719
2002 DNMT3B cooperates with DNMT1 to maintain DNA methylation and gene silencing in human cancer cells; disruption of both DNMT1 and DNMT3B reduced genomic methylation by >95%, demethylated repeated sequences, abolished IGF2 imprinting, and relieved p16INK4a silencing, whereas loss of DNMT3B alone reduced methylation by less than 3%. Targeted gene disruption in colorectal cancer cells, methyltransferase activity assays, bisulfite sequencing, gene expression analysis Nature High 11932749
2004 DNMT3L stimulates the DNA methylation activity of Dnmt3b (and Dnmt3a) approximately 1.5–3-fold through a direct protein–protein interaction; the C-terminal half of DNMT3L is responsible for this stimulation, and DNMT3L cannot bind DNA directly, indicating the effect is on catalytic activity rather than DNA targeting. In vitro methyltransferase activity assays, direct binding assays, domain deletion analysis The Journal of biological chemistry High 15105426
2007 Dnmt3a and Dnmt3b form a native complex in embryonic stem cells, directly interact and mutually stimulate each other's methyltransferase activity both in vitro and in vivo (stimulatory effect is independent of catalytic activity), and synergistically methylate the Oct4 and Nanog promoters during differentiation. Native complex purification from ES cells, Co-IP, in vitro methylation assays with catalytic mutants, bisulfite sequencing in differentiating cells and embryos Molecular and cellular biology High 17938196
2008 miR-148 represses DNMT3B expression through a target site in the protein-coding region (present in splice variants Dnmt3b1, Dnmt3b2, Dnmt3b4 but not Dnmt3b3); mutation of the target site abolished regulation, and Dnmt3b3 (lacking the site) is resistant to miR-148-mediated repression. miRNA overexpression and shRNA knockdown, site-directed mutagenesis of target site, mRNA/protein quantification RNA Medium 18367714
2009 The RNA-binding protein HuR binds the 3'UTR of DNMT3B mRNA, stabilizes it, and increases DNMT3B protein levels and global DNA methylation; cisplatin treatment triggers dissociation of the HuR–DNMT3B mRNA complex, promoting DNMT3B mRNA decay and reducing global methylation. Endogenous HuR RNP immunoprecipitation, in vitro biotinylated RNA pulldown/western blot, mRNA stability assays, global methylation analysis Nucleic acids research Medium 19270063
2010 DNMT3B associates with NEDD8-modified proteins in vivo, preferentially interacts with NEDDylated CUL4A (among cullins CUL1–5), and NEDD8 enhances DNMT3B-dependent DNA methylation; DNMT3B recruits CUL4A and NEDD8 to chromatin at a repressed promoter. Co-immunoprecipitation, in vitro direct binding assay with NEDD8, chromatin immunoprecipitation, deletion of Dnmt3b in cancer cell line The Journal of biological chemistry Medium 20847044
2012 DNMT3A and DNMT3B function as redox-dependent DNA 5-hydroxymethylcytosine dehydroxymethylases in vitro, directly converting 5-hmC to cytosine; the catalytic methylation sites of these enzymes are required for 5-hmC dehydroxymethylation activity. In vitro biochemical dehydroxymethylation assay, active-site mutagenesis The Journal of biological chemistry Medium 22898819
2013 Catalytically inactive DNMT3B3 modestly stimulates DNMT3A and counteracts DNMT3L stimulation; catalytically inactive DNMT3B4 significantly inhibits de novo DNA methylation by active DNMT3 enzymes by reducing their DNA-binding affinity. Both inactive isoforms also drive distinct chromatin compaction and H3K9me3 patterns. Biochemical in vitro methylation assays, DNA binding affinity assays, immunocytochemistry for H3K9me3 PloS one Medium 23894490
2016 DNMT3B loss in melanoma results in hypomethylation of the miR-196b promoter, increased miR-196b expression, which directly targets the mTORC2 component RICTOR, reducing mTORC2 activation and suppressing melanoma formation in a Braf/Pten mouse model. Conditional knockout mouse model, bisulfite sequencing of miR-196b promoter, miR-196b target validation (luciferase/western blot), genetic epistasis with RICTOR Cell reports Medium 26923591
2016 Catalytically inactive DNMT3B isoforms stimulate gene body methylation and re-methylation after demethylation-inhibitor treatment independently of their own catalytic activity, functioning as accessory proteins analogous to DNMT3L to recruit DNMT3A in somatic cells. Cellular re-methylation assays after 5-aza treatment, catalytic mutant isoform expression, genome-wide methylation analysis Nature communications Medium 27121154
2016 In human epidermal stem cells, Dnmt3b binds active enhancers in an H3K36me3-dependent manner and promotes DNA methylation along enhancer bodies; Dnmt3b depletion inactivates target enhancers and impairs epidermal stem cell function. ChIP-seq for endogenous Dnmt3a/3b, RRBS methylation analysis, enhancer RNA measurement, shRNA depletion with stem cell functional assays Cell stem cell Medium 27476967
2017 DNMT3B preferentially mediates non-CpG methylation of REST-targeted RE1 sequences in developing mouse hearts; loss of DNMT3B reduces non-CpG methylation at RE1 sites, decreases REST occupancy, and releases transcriptional suppression of adult cardiac genes. Mouse genetic models (Dnmt3b KO), bisulfite sequencing (CpG and non-CpG), ChIP for REST occupancy, gene expression analysis Nucleic acids research Medium 27956497
2019 Catalytically inactive Dnmt3b restores the majority of methylation and expression changes in Dnmt3b-null embryos, rescuing embryonic lethality, demonstrating that Dnmt3b functions as an accessory cofactor supporting other DNMTs; Dnmt3b also directly represses Wnt9b as a transcriptional repressor independent of its catalytic activity. Knock-in of catalytically inactive Dnmt3b in mice, genome-wide methylation, transcriptome analysis, rescue of embryonic lethality Nature communications High 31558711
2020 Comprehensive structural and enzymological analysis revealed that a hydrogen bond in the catalytic loop of DNMT3B causes lower CpG specificity than DNMT3A; interplay of the target recognition domain and homodimeric interface fine-tunes distinct target selection, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. Crystal structures, in vitro methylation activity assays, site-directed mutagenesis, cellular methylation profiling Nature communications High 32620778
2020 Cryo-EM structure of DNMT3A2–DNMT3B3–nucleosome ternary complex showed that the catalytic-like domain of accessory DNMT3B3 binds the acidic patch of the nucleosome core, orienting DNMT3A2 toward linker DNA; steric constraints suggest nucleosomal DNA must be repositioned for methylation. Cryo-electron microscopy structure determination, functional validation of binding Nature High 32968275
2020 DNMT3B catalytic domain methylation rates at non-CpG sites are more strongly affected by flanking sequences than at CpG sites; T775 has an essential dynamic role in the catalytic mechanism; six residues (N652, N656, N658, K777, N779, R823) in the DNA-binding interface equalize methylation rates across favored and disfavored sequence contexts. In vitro methylation of substrate pools with randomized flanking sequences, mutagenesis of active-site and interface residues Nucleic acids research High 33105482
2020 The catalytically inactive Dnmt3b3 isoform positively regulates de novo methylation by Dnmt3a and Dnmt3b (preferring Dnmt3b), is as potent as Dnmt3L in stimulating activities of Dnmt3a2 and Dnmt3b2 in vitro, and forms a 2:2 complex with Dnmt3a2; rescue experiments in triple-KO mESCs confirm Dnmt3b3 preferentially supports Dnmt3b2 over Dnmt3a2. In vitro methylation activity assays, stoichiometry analysis, rescue experiments in Dnmt3a/3b/3l triple-KO mESCs, genome-wide methylation Genes & development High 33004415
2016 Dnmt3b-C methylates DNA by a non-cooperative (processive) mechanism, in contrast to the cooperative mechanism of Dnmt3a-C; manipulations at the predicted dimer interface (including the R829H mutation analogous to the AML-associated R882H in DNMT3A) do not affect Dnmt3b-C activity or processivity, indicating dimer interface interactions play a limited role in regulating Dnmt3b. In vitro methylation kinetics assays distinguishing cooperativity from processivity, site-directed mutagenesis (R829H), buffer acidification experiments Biochemistry High 27768276
2022 Cryo-EM structure of the DNMT3B methyltransferase homo-oligomer reveals an FF interface whose interplay with the catalytic loop confers conformation and activity distinct from the DNMT3B–DNMT3L heterotetramer; ICF mutations at the FF interface impair DNA binding and heterochromatin targeting of DNMT3B, reducing DNA methylation in cells. Cryo-EM structure of homo-oligomer, biochemical DNA binding assays, cellular ChIP and methylation analyses with ICF mutants Nature communications High 35869095
2023 Cryo-EM structures of DNMT3B under various oligomerization states reveal that the ADD domain interacts with the MTase domain to form an autoinhibitory conformation; the PWWP domain allosterically regulates DNMT3B tetramer assembly; ADD-H3K4me0 and PWWP-H3K36me3 bindings differentially impact DNMT3B activity; oligomerization is coupled to folding of substrate-binding sites. Cryo-EM structure determination under multiple oligomerization states, biochemical activity assays, domain interaction analyses Nucleic acids research High 37941146
2018 Dnmt3b deletion in mesenchymal progenitor cells (Prx1-Cre) impairs fracture repair and chondrogenic/osteogenic differentiation; Dnmt3b directly binds two sites in the Rbpjκ promoter/gene body (confirmed by ChIP), repressing Notch signaling; Rbpjκ inhibition restored MPC differentiation in Dnmt3b-null cells. Conditional KO mice (Prx1-Cre), ChIP assay for Dnmt3b binding to Rbpjκ, luciferase reporter assay, in vitro differentiation assays, pharmacological Rbpjκ inhibition rescue JCI insight Medium 32051335
2014 Dnmt3b combined loss with Dnmt3a in HSCs synergistically enhances self-renewal and blocks differentiation more severely than Dnmt3a loss alone; the predominant Dnmt3b isoform in adult HSCs is catalytically inactive yet its residual activity in Dnmt3a-null HSCs drives some differentiation and generates paradoxical CpG island hypermethylation; combined Dnmt3a/3b loss activates β-catenin signaling. Conditional KO mice (alone and combined), HSC transplantation assays, whole-genome bisulfite sequencing, pathway analysis Cell stem cell High 25130491
2023 DNMT3B (not DNMT3A or DNMT3L) is specifically required in placental trophoblast lineages to silence germline genes and for formation of the maternal-fetal interface in the placental labyrinth; Sox2-Cre deletion of Dnmt3b only in the embryo (sparing placenta) rescued placental phenotype and embryonic lethality, demonstrating that the embryonic lethality of Dnmt3b-null mice is primarily caused by placental defects. Conditional KO using Sox2-Cre vs global KO, whole-genome bisulfite sequencing, transcriptome analysis, histology of placenta Nature communications High 36690623
2024 DNMT1 and DNMT3B (but not DNMT3A) cooperate to maintain DNA methylation; inducible DNMT1 degradation in human cells causes progressive passive demethylation, and loss of DNAme is accompanied by reversible changes in heterochromatin organization, genome compartmentalization, and peripheral localization. Inducible DNMT1 degradation (dTAG system), whole-genome bisulfite sequencing, Hi-C, lamina-associated domain analysis, live imaging The Journal of cell biology Medium 38376465
2019 Mahanine induces proteasomal degradation of DNMT3B (and DNMT1) via Akt inactivation; Akt physically interacts with DNMT3B, and disruption of this interaction (by mahanine or wortmannin) leads to DNMT3B degradation; constitutively active Akt prevents mahanine-induced DNMT3B loss, linking Akt signaling to DNMT3B protein stability. Co-immunoprecipitation of Akt–DNMT3B interaction, proteasome inhibitor rescue (MG132), constitutively active Akt overexpression, ubiquitination detection Molecular cancer Medium 24001151
2017 Rbm10-mediated alternative splicing controls the ratio of catalytically active Dnmt3b2 to inactive Dnmt3b3; Rbm10 deficiency increases Dnmt3b2 expression, leading to hypermethylation of NF-κB-responsive promoters and reduced NF-κB recruitment, thereby suppressing inflammatory gene expression. Rbm10 knockout mouse model and cell lines, RT-PCR for isoform ratios, bisulfite sequencing of NF-κB target promoters, ChIP for NF-κB occupancy, overexpression of Dnmt3b2 International immunology Medium 29309623
2022 DNMT3B dysfunction (KO or ICF mutations) leads to reduced steady-state (peri-)centromeric R-loops, which become susceptible to XPG/XPF endonuclease cleavage generating DNA breaks at centromeric satellite repeats; error-prone end-joining repairs these DSBs, causing chromosomal instability. DNMT3B KO cells and ICF patient cells, genome-wide ChIP-seq mapping DNA damage sites, R-loop immunofluorescence, endonuclease inhibition experiments, end-joining repair analysis Cell death & disease Medium 35688824

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 4577 10555141
2002 DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 1015 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 577 10588719
2008 miR-148 targets human DNMT3b protein coding region. RNA (New York, N.Y.) 435 18367714
2004 DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. The Journal of biological chemistry 347 15105426
2005 Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. Journal of neuroscience research 317 15672446
2014 Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem cells. Cell stem cell 281 25130491
2007 Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog. Molecular and cellular biology 198 17938196
2016 Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis. Cell stem cell 172 27476967
2002 Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mechanisms of development 169 12351185
2020 Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nature communications 154 32620778
2006 Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertility and sterility 145 17081533
2012 The mammalian de novo DNA methyltransferases DNMT3A and DNMT3B are also DNA 5-hydroxymethylcytosine dehydroxymethylases. The Journal of biological chemistry 128 22898819
2016 DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells. Nature communications 114 27121154
2005 De novo DNA methyltransferases Dnmt3a and Dnmt3b primarily mediate the cytotoxic effect of 5-aza-2'-deoxycytidine. Oncogene 109 15735669
2003 Double RNA interference of DNMT3b and DNMT1 enhances DNA demethylation and gene reactivation. Cancer research 104 14559786
2019 Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia. Biomarker insights 98 31105426
2011 Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas. Journal of neuro-oncology 97 21229291
2016 Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation. Oncotarget 94 26942697
2013 Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells. Molecular cancer 94 24001151
2020 Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B. Nature 93 32968275
2006 Dynamic expression of DNMT3a and DNMT3b isoforms during male germ cell development in the mouse. Developmental biology 92 16725135
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 86 30718452
2018 DNMT3B Functions: Novel Insights From Human Disease. Frontiers in cell and developmental biology 84 30406101
2016 DNA methylation by DNMT1 and DNMT3b methyltransferases is driven by the MUC1-C oncoprotein in human carcinoma cells. Oncogene 79 27212035
2015 miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1. Oncotarget 75 26497367
2023 Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B. Nature communications 69 36690623
2016 Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases. Advances in experimental medicine and biology 68 27826835
2022 m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency. Clinical and translational medicine 62 35340126
2016 DNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR. Cell reports 61 26923591
2021 FOXC1 promotes HCC proliferation and metastasis by Upregulating DNMT3B to induce DNA Hypermethylation of CTH promoter. Journal of experimental & clinical cancer research : CR 59 33522955
2020 The inactive Dnmt3b3 isoform preferentially enhances Dnmt3b-mediated DNA methylation. Genes & development 59 33004415
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
2006 Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA. Journal of biochemistry 59 16567415
2022 DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy. Frontiers in cell and developmental biology 57 35620052
2012 Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient. Epigenetics 57 22595875
2016 DNMT1, DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis. EBioMedicine 54 27789275
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
2017 DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos. Journal of molecular histology 53 29027601
2007 Age and gender affect DNMT3a and DNMT3b expression in human liver. Cell biology and toxicology 53 17929180
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
2013 Inactive DNMT3B splice variants modulate de novo DNA methylation. PloS one 49 23894490
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
2018 Telomerase reverse transcriptase regulates DNMT3B expression/aberrant DNA methylation phenotype and AKT activation in hepatocellular carcinoma. Cancer letters 48 30017965
2009 The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA. Nucleic acids research 47 19270063
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 41 34175897
2020 Induction of DNMT3B by PGE2 and IL6 at Distant Metastatic Sites Promotes Epigenetic Modification and Breast Cancer Colonization. Cancer research 41 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
2011 DNMT3B gene amplification predicts resistance to DNA demethylating drugs. Genes, chromosomes & cancer 38 21484930
2011 Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency. Journal of virology 37 22072770
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
2019 Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions. Nature communications 33 31558711
2018 Targets and genomic constraints of ectopic Dnmt3b expression. eLife 33 30468428
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
2012 Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma. Cancer research 33 22815530
2022 Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases. Advances in experimental medicine and biology 31 36350506
2017 Rbm10 regulates inflammation development via alternative splicing of Dnmt3b. International immunology 31 29309623
2023 Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance. Journal of translational medicine 29 37705098
2022 piRNA-6426 increases DNMT3B-mediated SOAT1 methylation and improves heart failure. Aging 29 35354120
2014 Dnmt3b Prefers Germ Line Genes and Centromeric Regions: Lessons from the ICF Syndrome and Cancer and Implications for Diseases. Biology 29 25198254
2021 HOTAIR suppresses PTEN via DNMT3b and confers drug resistance in acute myeloid leukemia. Hematology (Amsterdam, Netherlands) 28 33538241
2020 Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory. Molecular brain 28 32183852
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
2021 DNMT3A and DNMT3B Targeting as an Effective Radiosensitizing Strategy in Embryonal Rhabdomyosarcoma. Cells 25 34831178
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
2022 DNMT3b protects centromere integrity by restricting R-loop-mediated DNA damage. Cell death & disease 24 35688824
2020 miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer. Bioscience reports 24 32065219
2020 Dnmt3a and Dnmt3b-Decommissioned Fetal Enhancers are Linked to Kidney Disease. Journal of the American Society of Nephrology : JASN 24 32127410
2020 Complex DNA sequence readout mechanisms of the DNMT3B DNA methyltransferase. Nucleic acids research 24 33105482
2018 Reduced Self-Diploidization and Improved Survival of Semi-cloned Mice Produced from Androgenetic Haploid Embryonic Stem Cells through Overexpression of Dnmt3b. Stem cell reports 24 29396184
2018 Ablation of Dnmt3b in chondrocytes suppresses cell maturation during embryonic development. Journal of cellular biochemistry 24 29637597
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
2021 Pterostilbene leads to DNMT3B-mediated DNA methylation and silencing of OCT1-targeted oncogenes in breast cancer cells. The Journal of nutritional biochemistry 22 34242723
2020 Dnmt3b ablation impairs fracture repair through upregulation of Notch pathway. JCI insight 22 32051335
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
2012 Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork. Epigenetics 21 22847467
2022 Akebia Saponin D Inhibits the Inflammatory Reaction by Inhibiting the IL-6-STAT3-DNMT3b Axis and Activating the Nrf2 Pathway. Molecules (Basel, Switzerland) 20 36234773
2021 Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 33714108
2021 UXT, a novel DNMT3b-binding protein, promotes breast cancer progression via negatively modulating lncRNA MEG3/p53 axis. Molecular therapy oncolytics 20 35229028
2019 Epigenetic and therapeutic implications of dnmt3b in temporomandibular joint osteoarthritis. American journal of translational research 20 30972197
2024 Tunable DNMT1 degradation reveals DNMT1/DNMT3B synergy in DNA methylation and genome organization. The Journal of cell biology 19 38376465
2022 RAMP2-AS1 inhibits CXCL11 expression to suppress malignant phenotype of breast cancer by recruiting DNMT1 and DNMT3B. Experimental cell research 19 35390315
2022 Structure of DNMT3B homo-oligomer reveals vulnerability to impairment by ICF mutations. Nature communications 19 35869095
2021 De novo DNA methyltransferases DNMT3A and DNMT3B are essential for XIST silencing for erosion of dosage compensation in pluripotent stem cells. Stem cell reports 19 34416176
2020 Aberrant methylation of miR-124 upregulates DNMT3B in colorectal cancer to accelerate invasion and migration. Archives of physiology and biochemistry 19 32552060
2012 DNMT3B (C46359T) polymorphisms and immunoexpression of DNMT3b and DNMT1 proteins in oral lichen planus. Pathobiology : journal of immunopathology, molecular and cellular biology 19 22236544
2003 Genomic organization and promoter analysis of the Dnmt3b gene. Gene 19 12801642
2023 DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development. Molecular genetics and genomics : MGG 18 37020053
2023 Structural basis for the allosteric regulation and dynamic assembly of DNMT3B. Nucleic acids research 17 37941146

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