Affinage

MBD3

Methyl-CpG-binding domain protein 3 · UniProt O95983

Length
291 aa
Mass
32.8 kDa
Annotated
2026-04-28
68 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MBD3 is a core scaffold subunit of the Mi-2/NuRD chromatin remodeling and histone deacetylase complex that integrates transcription factor signals with epigenetic silencing at promoters, enhancers, and imprinting control regions. Unlike MBD2, MBD3 cannot bind methylated CpG DNA with high affinity due to His-30 and Phe-34 substitutions in its MBD domain; instead, this domain mediates protein–protein interactions with NuRD components HDAC1 and MTA2, and MBD3 preferentially associates with 5-hydroxymethylcytosine-marked loci in a Tet1-dependent manner (PMID:12124384, PMID:22196727, PMID:30980593). MBD3 recruits NuRD to specific genomic targets through interactions with transcription factors including unphosphorylated c-Jun, ZBTB7A/FBI-1, and PML-RARα, thereby controlling nucleosome occupancy, histone deacetylation, and DNA methylation states at genes governing pluripotency, lineage commitment, imprinting, and interferon signaling (PMID:21196933, PMID:23658227, PMID:16462733, PMID:17708683, PMID:32181805). MBD3 protein levels are regulated by ubiquitin-mediated proteasomal degradation catalyzed by E3 ligases MKRN3, Smek, and TRIM59, linking upstream signaling pathways—including Wnt/GSK3β—to NuRD complex assembly and target gene derepression during neurogenesis and tumorigenesis (PMID:28467410, PMID:34692086, PMID:41982165, PMID:40750707).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 Medium

    The question of whether MBD3 interacts with other MBD family members and DNA methyltransferases was addressed: MBD2 and MBD3 form homo- and heterodimers and co-localize with DNMT1 at replication foci, establishing MBD3 as part of a methylation-associated chromatin complex during S phase.

    Evidence Co-immunoprecipitation, in vitro binding, and immunofluorescence co-localization in mammalian cells

    PMID:10947852

    Open questions at the time
    • No reciprocal validation of DNMT1–MBD3 direct contact independent of MBD2
    • Functional consequence of MBD3–DNMT1 co-localization at replication foci not tested
  2. 2001 High

    Whether MBD3 is essential in vivo and whether it is required for NuRD integrity was unknown: Mbd3-knockout mice die at early embryogenesis and Mbd3-null cells fail to assemble a stable NuRD complex, establishing MBD3 as a non-redundant structural requirement for NuRD function.

    Evidence Gene targeting (knockout) with biochemical fractionation and genetic epistasis with Mbd2 in mice

    PMID:11274056

    Open questions at the time
    • Molecular basis of why MBD2 cannot compensate for MBD3 in NuRD assembly unclear
  3. 2002 High

    The paradox of why MBD3's MBD domain is conserved despite lacking methyl-CpG binding was resolved: His-30/Phe-34 substitutions ablate DNA binding, and the MBD instead mediates protein–protein interactions with HDAC1 and MTA2, repurposing the domain as a NuRD assembly scaffold. Concurrently, Aurora-A was identified as an M-phase kinase of MBD3, and p66α/β were mapped as direct MBD3-binding NuRD subunits.

    Evidence Mutagenesis with in vitro binding assays, GST pulldown, in vitro kinase assay, co-IP, yeast two-hybrid, immunofluorescence

    PMID:12124384 PMID:12183469 PMID:12354758

    Open questions at the time
    • Functional consequence of Aurora-A phosphorylation on NuRD activity or cell cycle progression not determined
    • Phosphorylation sites on MBD3 not mapped
  4. 2006 High

    Whether MBD2 and MBD3 exist in the same NuRD complex or form distinct entities was clarified: MBD2/NuRD and MBD3/NuRD are mutually exclusive assemblies, and MBD3/NuRD is specifically required for silencing pre-implantation genes and enabling lineage commitment of ES cells.

    Evidence Protein tagging with mass spectrometry in HeLa cells; Mbd3-knockout ES cell differentiation assays

    PMID:16428440 PMID:16462733

    Open questions at the time
    • How target specificity is determined for MBD3/NuRD versus MBD2/NuRD remains unresolved
    • Whether MBD3/NuRD acts primarily as a silencer or modulator of active genes was debated
  5. 2007 High

    MBD3's role extended beyond gene silencing: it was shown to be required for pluripotent ICM development in vivo, for maintaining imprint methylation at the H19 locus, and for regulating rRNA transcription by binding unmethylated rRNA promoters, revealing diverse genomic targets.

    Evidence Mbd3-knockout embryo analysis, RNAi with ChIP and bisulfite sequencing at H19 DMD, nucleolar localization and rRNA promoter ChIP

    PMID:17287250 PMID:17452452 PMID:17708683

    Open questions at the time
    • Whether MBD3 role at rRNA promoters involves canonical NuRD or a separate complex unclear
    • Mechanism of MBD3-dependent DNA demethylation at rRNA loci not established
  6. 2011 High

    Two key recruitment mechanisms were established: MBD3 preferentially binds 5hmC in a Tet1-dependent manner, co-localizing with Tet1 genome-wide and antagonizing Brg1 at shared promoters; separately, unphosphorylated c-Jun directly recruits MBD3/NuRD to AP-1 targets, with JNK phosphorylation serving as a molecular switch that releases repression.

    Evidence ChIP-seq, in vitro 5hmC binding assays, nucleosome occupancy analysis; reciprocal co-IP, conditional gut-specific Mbd3 knockout with c-Jun genetic epistasis rescue

    PMID:21196933 PMID:22196727

    Open questions at the time
    • 5hmC preference disputed by some groups; selectivity over unmodified cytosine debated
    • Whether c-Jun–MBD3 interaction is direct or bridged by other NuRD subunits not fully resolved
  7. 2013 High

    MBD3/NuRD was shown to localize predominantly at active CpG-rich promoters and enhancers, not exclusively at silent loci, and to regulate nucleosome occupancy at these sites, reframing NuRD as a modulator of active chromatin rather than a purely repressive complex.

    Evidence DamID and ChIP-seq genome-wide profiling in breast cancer cell lines with nucleosome occupancy analysis

    PMID:24385926

    Open questions at the time
    • Whether promoter-proximal nucleosome remodeling is a direct enzymatic activity of NuRD's CHD4 or an indirect consequence unclear
  8. 2017 High

    The first E3 ligase pathway controlling MBD3 stability was identified: Smek promotes MBD3 polyubiquitination and degradation, derepressing neurogenesis genes; genetic rescue of Smek-knockout neurogenesis defects by Mbd3 depletion established that MBD3 protein turnover is a regulatory node in cortical development.

    Evidence Co-IP, ubiquitination assay, ChIP, in vivo Smek1/2 knockout with Mbd3 knockdown rescue in mouse brain

    PMID:28467410

    Open questions at the time
    • Whether Smek acts as the direct E3 ligase or recruits another ligase not fully defined
    • Ubiquitination sites on MBD3 targeted by Smek not mapped
  9. 2018 High

    The specific NuRD subcomplex axis Gatad2a–Chd4–Mbd3 was identified as the critical barrier to naive pluripotency reestablishment, and MBD3's C-terminal D/E-rich domain was shown to function as a Z-DNA mimic that binds ADAR1's Zα domain, revealing an unexpected non-NuRD interaction.

    Evidence Genetic deletion of Gatad2a with reprogramming assays; biophysical (ITC/SPR) and biochemical (GST pulldown, co-IP) characterization of MBD3–ADAR1 interaction

    PMID:30122475 PMID:30304469

    Open questions at the time
    • Functional consequence of MBD3–ADAR1 interaction on RNA editing or innate immunity not tested
    • Whether Gatad2b can substitute for Gatad2a in NuRD repression of pluripotency not resolved
  10. 2019 High

    Structural resolution of MBD3-MBD bound to mCG DNA revealed that two conserved arginine fingers contact mCG and the Tyr-to-Phe substitution at position 34 is the primary determinant of weakened methyl-CpG affinity relative to MBD2.

    Evidence X-ray crystallography with mutagenesis and in vitro binding validation

    PMID:30980593

    Open questions at the time
    • No structure of full-length MBD3 or MBD3 within NuRD complex
    • Structural basis for 5hmC preference not addressed
  11. 2020 High

    Two additional E3 ubiquitin ligase pathways converging on MBD3 were identified: MKRN3 ubiquitinates MBD3 to displace it from the GNRH1 promoter (linking MBD3 to puberty timing), and MBD3 recruits NuRD to the STAT1 promoter in glioma stem cells to suppress interferon signaling.

    Evidence Co-IP with ubiquitination assay and Mkrn3-knockout mice; ChIP with knockdown and tumor xenograft models

    PMID:32181805 PMID:34692086

    Open questions at the time
    • Whether MKRN3-mediated MBD3 degradation occurs in normal hypothalamic neurons or only in overexpression systems
    • Whether MBD3's STAT1 regulation is NuRD-dependent or involves independent activity not fully excluded
  12. 2025 Medium

    Wnt signaling was connected to MBD3 stability through GSK3β-dependent ubiquitination, and TRIM59 was identified as a direct E3 ligase polyubiquitinating MBD3 at K41/K90/K92, establishing a network of degradation pathways controlling NuRD availability in neurogenesis and lung cancer.

    Evidence Wnt3a/DKK1 modulation with ubiquitination assays; TRIM59 co-IP with MS-mapped ubiquitination sites and in vivo tumor models

    PMID:40750707 PMID:41982165

    Open questions at the time
    • Whether GSK3β directly phosphorylates MBD3 to prime ubiquitination or acts indirectly not determined
    • Relationship between TRIM59, Smek, and MKRN3 pathways — whether they are redundant or context-specific — is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of MBD3's preferential 5hmC recognition, the architecture of the full MBD3/NuRD holocomplex, the functional significance of MBD3 liquid-liquid phase separation and ADAR1 interaction, and how multiple E3 ligase pathways are coordinated to regulate MBD3 levels in different cellular contexts.
  • No cryo-EM or crystal structure of MBD3-containing NuRD holocomplex
  • Functional role of MBD3 phase separation in chromatin regulation untested in cells
  • MBD3–ADAR1 interaction lacks demonstrated biological function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 3 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
ADAR1CHD4DNMT1GATAD2AGATAD2BHDAC1MBD2MTA2
Complex memberships
Mi-2/NuRD (MBD3/NuRD)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MBD3 fails to bind methylated DNA in murine cells and is a core component of the Mi-2/NuRD corepressor complex; Mbd3-/- mice die during early embryogenesis, and Mbd3-deficient cells fail to form a stable NuRD complex. Genetic interaction with Mbd2 was demonstrated by double-mutant analysis. Gene targeting (knockout), biochemical fractionation, genetic epistasis Genes & development High 11274056
2000 MBD2 and MBD3 form homo- and hetero-dimers in vitro and in vivo; the MBD2-MBD3 complex shows affinity for hemi-methylated DNA (not previously shown for any MBD family member). MBD2 and MBD3 co-localize with DNMT1 at replication foci in late S phase, and co-immunoprecipitation shows DNMT1 forms a complex with MBD2 and MBD3. Co-immunoprecipitation, in vitro binding assay, immunofluorescence co-localization Genes to cells Medium 10947852
2002 The MBD domain of human MBD3 cannot bind mCpG due to atypical residues His-30 and Phe-34; substitution H30K/F34Y restores mCpG binding in vitro but does not restore pericentromeric localization in cells. The MBD3 MBD domain is necessary and sufficient for binding to NuRD/Mi2 complex components HDAC1 and MTA2, indicating a protein-protein interaction role for this domain. In vitro binding assay with recombinant mutant proteins, immunofluorescence, GST pulldown The Journal of biological chemistry High 12124384
2002 MBD3 is phosphorylated in vivo during late G2 and early M phase. Aurora-A kinase phosphorylates MBD3 in vitro, physically associates with MBD3 in vivo by co-immunoprecipitation, and co-localizes with MBD3 and HDAC1 at centrosomes in early M phase. Stable FLAG-tagged expression, co-immunoprecipitation, in vitro kinase assay, immunofluorescence microscopy The Journal of biological chemistry High 12354758
2002 MBD3 directly interacts with p66alpha and p66beta (two NuRD subunits identified by yeast two-hybrid), and co-precipitates with MBD2 in vivo. Both p66 family members bind directly to MBD2 and MBD3, with p66alpha having two interaction domains and p66beta one. Yeast two-hybrid, co-immunoprecipitation, GST pulldown, confocal microscopy The Journal of biological chemistry Medium 12183469
2005 Dnmt3a physically interacts with Mbd3 in mouse lymphosarcoma cells; the N-terminal ATRX homology domain of Dnmt3a interacts with the methyl-CpG-binding domain of Mbd3 (GST pulldown). All three proteins (Dnmt3a, Mbd3, Brg1) are associated with the silent methylated MT-I promoter by ChIP, and Mbd3 and Dnmt3a specifically inhibit the methylated promoter in transient transfection assays. GST pulldown, co-immunoprecipitation, ChIP, transient transfection reporter assay Cancer research Medium 16322236
2006 MBD2 and MBD3 assemble into mutually exclusive, distinct Mi-2/NuRD-like complexes (MBD2/NuRD and MBD3/NuRD). DOC-1 is identified as a novel core subunit of both complexes. PRMT5 and its cofactor MEP50 are specific MBD2/NuRD interactors; PRMT5 methylates the RG-rich N-terminus of MBD2. Protein tagging, mass spectrometry, co-immunoprecipitation, ChIP Molecular and cellular biology High 16428440
2006 Mbd3-deficient embryonic stem cells fail to form a stable NuRD complex and cannot silence genes expressed before implantation; they exhibit LIF-independent self-renewal but fail to commit to developmental lineages, demonstrating Mbd3 is required for cell-fate commitment of pluripotent cells. Gene targeting (knockout), gene expression analysis, differentiation assays, biochemical fractionation Nature cell biology High 16462733
2007 MBD3 is bound to the H19 differentially methylated domain (DMD) by ChIP; RNAi-mediated depletion of MBD3 in mouse embryos activates paternal H19 expression, reduces DNA methylation at the H19 DMD, and reduces MTA-2 levels, demonstrating MBD3/NuRD is required for maintaining imprint control region methylation and silencing the paternal H19 allele. RNAi knockdown, ChIP, bisulfite sequencing, allele-specific expression analysis PLoS genetics High 17708683
2007 MBD3 is required for development of pluripotent inner cell mass cells in vivo; Mbd3-deficient ICMs fail to expand Oct4-positive pluripotent cells after implantation, and Mbd3 controls stage-specific gene expression patterns in pre- and peri-implantation embryos. Gene targeting, ex vivo ICM culture, immunofluorescence, gene expression analysis Development High 17287250
2007 MBD3 localizes to the nucleolus, co-localizes with upstream binding factor, and binds to unmethylated rRNA promoters. MBD3 knockdown causes increased methylation of the rRNA promoter and decreased RNA Pol I binding and pre-rRNA transcription; MBD3 overexpression decreases rRNA promoter methylation and induces demethylation of nonreplicating plasmids containing the rRNA promoter. siRNA knockdown, ChIP, bisulfite sequencing, immunofluorescence, plasmid demethylation assay Molecular and cellular biology Medium 17452452
2008 MBD3 facilitates Polycomb binding and histone H3K27 methylation at PML-RARa target genes (including RARbeta2) in acute promyelocytic leukemia; PML-RARa recruits the NuRD complex to target genes, and NuRD knockdown prevents histone deacetylation, chromatin compaction, DNA and histone methylation, and stable silencing. ChIP, siRNA knockdown, histone modification assays, differentiation assays Molecular and cellular biology Medium 18644863
2008 Evi1 interacts specifically with Mbd3b (not other MBD family members) through 40 amino acids adjacent to the MBD and requires the first three zinc fingers of Evi1; when associated with Mbd3 in the Mi-2/NuRD complex, Evi1 inhibits the histone deacetylation function of the complex. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, in vitro HDAC activity assay Biochemistry Medium 18500823
2008 MBD3 overexpression induces genomic DNA demethylation at specific targets, particularly promoter regions with intermediate CpG density, as revealed by methylated DNA immunoprecipitation coupled to promoter tiling microarray. MBD3 overexpression, mDIP-chip (methylated DNA immunoprecipitation + microarray) Gene Medium 18602768
2011 Mbd3 and Brg1 antagonistically regulate a common set of genes by controlling promoter nucleosome occupancy in ES cells. Mbd3 co-localizes with Tet1 and 5hmC in vivo, Mbd3 localization is Tet1-dependent, and Mbd3 preferentially binds 5hmC relative to 5-methylcytosine in vitro. Both Mbd3 and Brg1 are required for normal 5hmC levels in vivo. ChIP-seq, nucleosome occupancy assay, in vitro DNA binding assay, knockdown, genomic 5hmC quantification Cell High 22196727
2011 Unphosphorylated c-Jun interacts with Mbd3 and thereby recruits the NuRD repressor complex to AP-1 target promoters; JNK-mediated N-terminal phosphorylation of c-Jun prevents Mbd3 interaction, relieving repression. Gut-specific conditional deletion of mbd3 stimulates c-Jun activity, increases progenitor proliferation, and increases susceptibility to colitis-induced tumorigenesis; single allele inactivation of c-jun reverts these phenotypes. Co-immunoprecipitation, conditional knockout, ChIP, genetic epistasis (c-jun heterozygosity rescue), colon cancer cell knockdown Nature High 21196933
2013 FBI-1 (ZBTB7A) directly interacts with MBD3 in the nucleus; MBD3 is recruited to the CDKN1A promoter through FBI-1, enhancing transcriptional repression. MBD3 modulates interactions between FBI-1 and co-repressors (decreasing NCoR/SMRT interaction, increasing BCoR interaction), and recruits the Mi-2/NuRD-HDAC complex, DNMTs, and HP1 to the locus to mediate epigenetic silencing of p21WAF/CDKN1A. Co-immunoprecipitation, ChIP, transient transfection reporter assay, knockdown Nucleic acids research Medium 23658227
2013 MBD3 localizes at promoters, gene bodies, and enhancers of active genes in human breast cancer cells (MCF-7, MDA-MB-231), with preferential association at CpG-rich promoters marked by H3K4me3. MBD3 regulates nucleosome occupancy near promoters and in gene bodies. DamID, ChIP-seq, nucleosome occupancy analysis PLoS genetics High 24385926
2015 MBD3 forms a salt-dependent homodimeric association with chromatin loci in G1 phase. MBD3 co-localizes with DNMT1 and MBD2 during DNA maintenance methylation in S phase; insufficient MBD3 caused by siRNA results in global DNA hypermethylation and increased methylation of cell cycle gene promoter CpG islands. FLCS, PCH, FLIM-FRET, siRNA knockdown, bisulfite sequencing Nucleic acids research Medium 25753672
2016 Chromatin localization of Mbd2 and Mbd3 is highly overlapping in ES cells, and the two proteins are interdependent for chromatin association. Both are required for normal levels of cytosine methylation and hydroxymethylation in murine ES cells, and they regulate overlapping sets of genes also regulated by DNA methylation/hydroxymethylation factors. ChIP-seq, bisulfite sequencing, 5hmC quantification, knockdown/knockout eLife High 27849519
2017 Smek interacts with Mbd3 and promotes its polyubiquitylation and degradation, blocking recruitment of the repressive Mbd3/NuRD complex at neurogenesis-associated gene loci, increasing histone H3 acetylation, and promoting cortical neurogenesis. Overexpression of Mbd3 blocks neuronal differentiation of NPCs, and Mbd3 depletion rescues neurogenesis defects in Smek1/2 knockout mice. Co-immunoprecipitation, ubiquitylation assay, ChIP, knockout mouse, overexpression/knockdown PLoS biology High 28467410
2018 A specific NuRD subcomplex axis — Gatad2a-Chd4-Mbd3 — is critical for blocking reestablishment of naive pluripotency. Complete deletion of Gatad2a specifically disrupts Mbd3/NuRD repressive activity on the pluripotency circuitry without ablating somatic cell proliferation, and post-translational modifications of Mbd3/NuRD influence its interactions and assembly. Genetic deletion, co-immunoprecipitation, reprogramming assays, post-translational modification analysis Cell stem cell High 30122475
2018 The C-terminal D/E-rich domain of MBD3 acts as a Z-DNA mimic that interacts with the Zα domain of ADAR1 with high affinity; this interaction competes with Z-DNA for Zα binding. MBD3 dimerization via intermolecular interaction of the D/E-rich domain with its own MBD domain attenuates the Zα interaction. Co-immunoprecipitation confirmed the MBD3–ADAR1 interaction in vivo. GST pulldown, biophysical analysis (ITC/SPR), co-immunoprecipitation, DNA conformational assay Nucleic acids research Medium 30304469
2019 Crystal/structural analysis of MBD3-MBD bound to mCG-containing DNA reveals two conserved arginine fingers mediate mCG binding; the Tyr-to-Phe substitution at Phe34 of MBD3 (versus MBD2) is responsible for weaker mCG binding. MBD3-MBD can recognize mCG without orientation selectivity. X-ray crystallography, in vitro binding assays, mutagenesis The FEBS journal High 30980593
2020 MKRN3 (an E3 ubiquitin ligase) interacts with and ubiquitinates MBD3, disrupting MBD3 binding to the GNRH1 promoter and preventing recruitment of the DNA demethylase TET2. Genetic ablation of Mkrn3 accelerates puberty onset with increased GnRH1 production; this is mechanistically linked to MBD3-mediated epigenetic silencing of GNRH1. Co-immunoprecipitation, ubiquitination assay, genetic knockout, ChIP, DNA methylation analysis National science review High 34692086
2020 MBD3 recruits the NuRD complex to the STAT1 promoter in glioma stem-like cells to suppress STAT1 expression by histone deacetylation, enabling evasion of type I interferon suppression. MBD3 depletion induces p21 transcription, resensitizes GSCs to IFN suppression, and attenuates tumor growth. ChIP, knockdown, overexpression, animal tumor model, histone modification assays The Journal of experimental medicine Medium 32181805
2025 Canonical Wnt signaling regulates Mbd3 protein stability: Wnt3a activation increases Mbd3 levels; DKK1 inhibition reduces them. GSK3β overexpression promotes and depletion attenuates Mbd3 ubiquitination. Mbd3 downstream represses neurogenesis-associated genes by triggering NuRD complex assembly, promoting NPC stemness. Wnt pathway modulation, GSK3β overexpression/knockdown, ubiquitination assay, co-immunoprecipitation, gene expression analysis Experimental & molecular medicine Medium 40750707
2026 TRIM59 functions as the E3 ubiquitin ligase for MBD3, physically associating with the N-terminal MBD domain of MBD3 and catalyzing its polyubiquitination and proteasomal degradation; mass spectrometry mapping identifies ubiquitination sites at K41, K90, and K92. TRIM59-mediated MBD3 degradation derepresses HSF1 and HSF2, promoting lung adenocarcinoma progression. Co-immunoprecipitation, ubiquitination assay, mass spectrometry, knockdown/overexpression, in vivo tumor model Acta biochimica et biophysica Sinica Medium 41982165
2025 MBD2 and MBD3 undergo liquid-liquid phase separation (LLPS) through distinct homotypic and heterotypic interactions despite high sequence identity; DNA influences this process. MBD3 has differing residue patterns from MBD2 resulting in a distinct phase separation mechanism. In vitro LLPS assay, computational modeling, biophysical characterization The journal of physical chemistry. B Medium 40350613

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes & development 390 11274056
2011 Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 364 22196727
2006 The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nature cell biology 305 16462733
2006 MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Molecular and cellular biology 271 16428440
2002 The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2. The Journal of biological chemistry 141 12124384
2007 Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development (Cambridge, England) 139 17287250
2014 MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner. Cell stem cell 135 24835571
2000 MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes to cells : devoted to molecular & cellular mechanisms 120 10947852
2011 c-Jun N-terminal phosphorylation antagonises recruitment of the Mbd3/NuRD repressor complex. Nature 107 21196933
2008 MBD3, a component of the NuRD complex, facilitates chromatin alteration and deposition of epigenetic marks. Molecular and cellular biology 91 18644863
2013 MBD3 localizes at promoters, gene bodies and enhancers of active genes. PLoS genetics 90 24385926
1999 Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes. Mammalian genome : official journal of the International Mammalian Genome Society 90 10441743
2002 Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3. The Journal of biological chemistry 80 12183469
2020 MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3. National science review 64 34692086
2007 Maintenance of paternal methylation and repression of the imprinted H19 gene requires MBD3. PLoS genetics 63 17708683
2018 Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency. Cell stem cell 62 30122475
2005 Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells. Cancer research 56 16322236
2014 MBD2 and MBD3: elusive functions and mechanisms. Frontiers in genetics 55 25538734
2007 Epigenetic programming of the rRNA promoter by MBD3. Molecular and cellular biology 49 17452452
2002 MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase. The Journal of biological chemistry 47 12354758
2020 Glioma stem-like cells evade interferon suppression through MBD3/NuRD complex-mediated STAT1 downregulation. The Journal of experimental medicine 44 32181805
2019 Disruption of the MBD2-NuRD complex but not MBD3-NuRD induces high level HbF expression in human adult erythroid cells. Haematologica 43 31004025
2013 The proto-oncoprotein FBI-1 interacts with MBD3 to recruit the Mi-2/NuRD-HDAC complex and BCoR and to silence p21WAF/CDKN1A by DNA methylation. Nucleic acids research 41 23658227
2009 Mbd3, a component of NuRD/Mi-2 complex, helps maintain pluripotency of mouse embryonic stem cells by repressing trophectoderm differentiation. PloS one 38 19888462
2002 MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins MBD2 and MBD3: characterization of MBD3L1 as a testis-specific transcriptional repressor. Genomics 35 12504854
2005 MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing. The Journal of biological chemistry 32 15701600
2008 DNA demethylation induced by the methyl-CpG-binding domain protein MBD3. Gene 29 18602768
2015 Dissecting the behavior and function of MBD3 in DNA methylation homeostasis by single-molecule spectroscopy and microscopy. Nucleic acids research 26 25753672
2016 DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells. eLife 25 27849519
2017 Smek promotes corticogenesis through regulating Mbd3's stability and Mbd3/NuRD complex recruitment to genes associated with neurogenesis. PLoS biology 24 28467410
2019 MBD3/NuRD loss participates with KDM6A program to promote DOCK5/8 expression and Rac GTPase activation in human acute myeloid leukemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 30668141
2017 Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program. The Journal of experimental medicine 23 28899870
2022 MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2. British journal of cancer 22 35501390
2016 MBD3 mediates epigenetic regulation on EPAS1 promoter in cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 27465550
2008 Myeloid transforming protein Evi1 interacts with methyl-CpG binding domain protein 3 and inhibits in vitro histone deacetylation by Mbd3/Mi-2/NuRD. Biochemistry 21 18500823
2019 Structural analyses reveal that MBD3 is a methylated CG binder. The FEBS journal 18 30980593
2019 Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial-mesenchymal plasticity and tumor metastasis. Oncogene 18 31666683
2003 Differential expression of methyl CpG-binding domain containing factor MBD3 in the developing and adult rat brain. Journal of neurobiology 18 12672019
2016 MiR-134-Mbd3 axis regulates the induction of pluripotency. Journal of cellular and molecular medicine 16 26929159
2004 Xenopus MBD3 plays a crucial role in an early stage of development. Developmental biology 15 15063177
2017 MBD3 inhibits formation of liver cancer stem cells. Oncotarget 13 27894081
2014 Construction of eukaryotic expression vector with mBD1-mBD3 fusion genes and exploring its activity against influenza A virus. Viruses 13 24632574
2004 Genetic and epigenetic analyses of MBD3 in colon and lung cancer. British journal of cancer 12 15138480
2013 Removing reprogramming roadblocks: Mbd3 depletion allows deterministic iPSC generation. Cell stem cell 11 24094318
2021 Functional Analysis of Non-Genetic Resistance to Platinum in Epithelial Ovarian Cancer Reveals a Role for the MBD3-NuRD Complex in Resistance Development. Cancers 10 34359703
2024 MBD3 promotes epithelial-mesenchymal transition in gastric cancer cells by upregulating ACTG1 via the PI3K/AKT pathway. Biological procedures online 9 38178023
2023 MBD3 as a Potential Biomarker for Colon Cancer: Implications for Epithelial-Mesenchymal Transition (EMT) Pathways. Cancers 9 37370795
2018 The C-terminal D/E-rich domain of MBD3 is a putative Z-DNA mimic that competes for Zα DNA-binding activity. Nucleic acids research 9 30304469
2019 Overexpression of MBD3 Improves Reprogramming of Cloned Pig Embryos. Cellular reprogramming 6 31393170
2018 Mbd3 Promotes Reprogramming of Primary Human Fibroblasts. International journal of stem cells 6 30497130
2016 MBD3 expression and DNA binding patterns are altered in a rat model of temporal lobe epilepsy. Scientific reports 6 27650712
2016 Regulatory landscape and clinical implication of MBD3 in human malignant glioma. Oncotarget 6 27835581
2025 Uncovering the Molecular Interactions Underlying MBD2 and MBD3 Phase Separation. The journal of physical chemistry. B 5 40350613
2020 Methyl-CpG-binding domain 3 (Mbd3) is an important regulator for apoptosis in mouse embryonic stem cells. American journal of translational research 5 33437388
2016 High-quality ChIP-seq analysis of MBD3 in human breast cancer cells. Genomics data 5 26981404
2022 Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naïve pluripotency under inhibition of protein kinase C. Cell death discovery 4 35915078
2023 MBD3 Regulates Male Germ Cell Division and Sperm Fertility in Arabidopsis thaliana. Plants (Basel, Switzerland) 3 37514268
2020 Thyroid hormone activates Xenopus MBD3 gene via an intronic TRE in vivo. Frontiers in bioscience (Landmark edition) 3 31585895
2025 LncRNA16 inhibits pyroptosis and promotes platinum resistance in non-small cell lung cancer by sponging miRNA1827 to regulate MBD3/GSDME expression. Cancer cell international 2 40413520
2024 Uncovering the molecular interactions underlying MBD2 and MBD3 phase separation. bioRxiv : the preprint server for biology 2 38746378
2009 MBD3 mutations are not responsible for ICR1 hypomethylation in Silver-Russell syndrome. European journal of medical genetics 2 20004753
2021 Expression of mBD4, mBD3 and CRAMP during type II collagen-induced arthritis/CIA and their association with inflammation and bone-remodeling markers. Experimental and molecular pathology 1 34592200
2026 MBD3 increased expression by BRD4 and facilitated castration-resistant prostate cancer cell proliferation by inhibiting PTEN. Discover oncology 0 41663664
2026 The role of MBD3 in cell biology and disease: Recent advances and future directions. Experimental cell research 0 41933571
2026 Ubiquitin-dependent degradation of MBD3 by TRIM59 promotes lung adenocarcinoma. Acta biochimica et biophysica Sinica 0 41982165
2025 Canonical Wnt signaling regulates Mbd3 protein stability during neurogenesis. Experimental & molecular medicine 0 40750707
2025 The role of Methyl-CpG binding domain 3 (Mbd3) protein in epileptogenesis. PloS one 0 41060926
2023 Clinical significance of serum MBD3 detection in girls with central precocious puberty. Open medicine (Warsaw, Poland) 0 37426049