Affinage

MBD1

Methyl-CpG-binding domain protein 1 · UniProt Q9UIS9

Length
605 aa
Mass
66.6 kDa
Annotated
2026-06-10
52 papers in source corpus 32 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MBD1 is a methyl-CpG-binding transcriptional repressor that translates DNA methylation status into heritable chromatin silencing by reading methylated DNA through its MBD domain and assembling context-specific repressive complexes via a C-terminal transcriptional repression domain (TRD) (PMID:11371345, PMID:10648624, PMID:20378711). The MBD folds into an alpha/beta sandwich that recognizes methyl groups and CG sequence through a conserved hydrophobic patch, and is necessary and sufficient for targeting MBD1 to methylated loci; it preferentially engages tandem symmetrically methylated CpG sites (PMID:11371345, PMID:10581239, PMID:20378711). Alternative splicing generates CXXC3-containing isoforms that additionally bind unmethylated CpG, enabling methylation-independent repression and heterochromatin localization (PMID:10454587, PMID:10866667, PMID:15060159). Silencing is enacted by recruiting histone-modifying machinery: MBD1 couples H3K9 methylation to histone deacetylation through Suv39h1/HP1 and through HDAC3, and assembles an MBD1·MCAF1(ATF7IP)·SETDB1 complex required for heterochromatin formation, including an S-phase CAF-1/MBD1/SETDB1 complex that propagates H3K9 methylation during replication-coupled chromatin assembly (PMID:10648624, PMID:12711603, PMID:12665582, PMID:15327775, PMID:15691849, PMID:24810720). SUMOylation of MBD1 by PIAS1/3 antagonizes SETDB1 recruitment, providing a switch that modulates the silencing output (PMID:17066076). Through these activities MBD1 maintains X-inactivation and Aire-dependent thymic tolerance, and directs neural and neuronal gene programs by repressing Fgf-2, miR-184, and Oprm1 via DNA-methylation-dependent and DNMT3a/SUV39H1-coupled mechanisms (PMID:18689796, PMID:20452318, PMID:24464130, PMID:25028596, PMID:30266739, PMID:41090695). Beyond transcription, MBD1 acts at the replication fork, recruiting PARP1 to stabilize stalled forks and limit transcription-replication conflicts, and its CXXC3 domain tunes TET1-mediated 5mC oxidation at heterochromatin (PMID:28449087, PMID:35709470, PMID:37949945).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Establishing how MBD1 physically reads its substrate, the free and methylated-DNA-bound MBD structures defined the alpha/beta-sandwich fold and the conserved residues that recognize methyl-CpG, providing the structural basis for methylation reading.

    Evidence NMR solution structures of free and methylated-DNA-bound MBD with site-directed mutagenesis

    PMID:10581239 PMID:11371345

    Open questions at the time
    • Structures of full-length MBD1 or its complexes not determined
    • Does not address how MBD selectivity is tuned across genomic contexts
  2. 1999 High

    Discovery that alternative splicing produces CXXC3-containing isoforms binding unmethylated DNA showed MBD1 represses both methylated and unmethylated promoters through distinct domains, revealing two parallel targeting modes.

    Evidence GFP-isoform transfection in methylation-deficient and mammalian cells, reporter assays, EMSA

    PMID:10454587 PMID:10866667

    Open questions at the time
    • Relative in vivo contributions of MBD vs CXXC3 targeting not resolved here
    • Tissue-specific isoform usage unknown
  3. 2000 High

    Mapping the C-terminal TRD and its HDAC-inhibitor sensitivity established MBD1 as an active repressor dependent on histone deacetylation, distinct from the MeCP1 complex.

    Evidence Reporter assays, trichostatin A treatment, immunofluorescence, co-immunoprecipitation

    PMID:10648624

    Open questions at the time
    • Direct deacetylase partner not identified at this stage
    • Mechanism of repression at a distance unexplained
  4. 2003 High

    Identification of Suv39h1/HP1, CAF-1 p150, and the MCAF mediator as MBD1 partners explained how MBD1 couples DNA methylation reading to H3K9 methylation, heterochromatin, and Sp1-blocking repression.

    Evidence GST pulldown, reciprocal Co-IP, yeast two-hybrid, immunofluorescence colocalization, dominant-negative overexpression, reporter assays

    PMID:12665582 PMID:12697822 PMID:12711603

    Open questions at the time
    • How these complexes are temporally coordinated not yet defined
    • Stoichiometry and exclusivity of complexes unknown
  5. 2004 High

    The S-phase-specific CAF-1/MBD1/SETDB1 complex showed MBD1 propagates H3K9 methylation during replication-coupled chromatin assembly, linking methylation maintenance to chromatin inheritance.

    Evidence Co-IP, ChIP, siRNA knockdown, S-phase cell fractionation

    PMID:15327775

    Open questions at the time
    • Direct demonstration of mark inheritance across generations not shown
    • Genome-wide scope of affected loci limited
  6. 2004 High

    Demonstrating that CXXC3 binds nonmethylated CpG in vivo clarified the basis for methylation-independent heterochromatin localization and repression of unmethylated targets.

    Evidence Domain-mutant transfection, DNA binding assays, fluorescence microscopy in methylation-deficient cells

    PMID:15060159

    Open questions at the time
    • Endogenous nonmethylated targets not catalogued
    • Interplay with MBD-based targeting unresolved
  7. 2005 High

    Defining MCAF1/MCAF2 as bridging factors linking MBD1, SETDB1, and Sp1 established the MBD1·MCAF1·SETDB1 complex as the core machinery for heterochromatic domain formation.

    Evidence Co-IP, in vitro binding, siRNA knockdown, immunofluorescence with domain mutants, reporter assays

    PMID:15691849

    Open questions at the time
    • Distinct roles of MCAF1 vs MCAF2 not separated
    • Recruitment hierarchy at native loci unclear
  8. 2006 High

    Discovery of SUMOylation by PIAS1/3 and SUMO-dependent MCAF1 binding revealed a post-translational switch controlling whether MBD1 assembles the repressive SETDB1 complex.

    Evidence In vivo sumoylation assays, site-directed mutagenesis of acceptor lysines, Co-IP, siRNA knockdown, reporter assays, immunofluorescence

    PMID:16757475 PMID:17066076

    Open questions at the time
    • Signals controlling MBD1 SUMOylation dynamics unknown
    • How SUMO simultaneously blocks SETDB1 yet aids MCAF1 binding is mechanistically unreconciled
  9. 2006 High

    Placing an HDAC3-MBD1 complex downstream of PML-RARalpha connected MBD1 to oncogenic transcriptional silencing and a block to hematopoietic differentiation.

    Evidence ChIP, siRNA knockdown, dominant-negative MBD1 expression, differentiation assays

    PMID:16432238

    Open questions at the time
    • Direct MBD1-HDAC3 contact details limited
    • Generality beyond PML-RARalpha targets not tested
  10. 2007 High

    Linking MBD1 to PRC1 components Ring1b and hPc2 via its CXXC domains extended MBD1 silencing to Polycomb-controlled HOXA loci.

    Evidence Co-IP, ChIP, siRNA knockdown, domain-mutant immunofluorescence, 5-azadeoxycytidine treatment

    PMID:17428788

    Open questions at the time
    • Direct vs indirect nature of PRC1 association not fully resolved
    • Genome-wide overlap with Polycomb domains undefined
  11. 2008 High

    Identifying Mbd1 repression of Fgf-2 in adult neural stem cells assigned MBD1 a physiological role in neuronal differentiation via methylation-dependent silencing.

    Evidence ChIP, bisulfite sequencing, methylation inhibitor, siRNA knockdown, overexpression in NSPCs

    PMID:18689796

    Open questions at the time
    • How Mbd1 loss leads to promoter hypomethylation not explained
    • Full neural target set not defined
  12. 2010 High

    The MBD1→miR-184→Numbl axis and refined ChIP/in vitro mapping established that the MBD domain is the principal in vivo targeting determinant and that MBD1 controls neural stem cell fate through a miRNA circuit.

    Evidence ChIP, luciferase 3'-UTR reporters, miRNA gain/loss, rescue experiments, in vitro domain binding, MBD point mutants

    PMID:20378711 PMID:20452318

    Open questions at the time
    • When CXXC3 targeting becomes functionally relevant remains unclear
    • Broader miRNA targets of MBD1 not surveyed
  13. 2013 High

    Showing the TRD is intrinsically disordered yet binds distinct partners (MPG, MCAF1, HDAC3) explained how a single repression module recruits multiple effectors.

    Evidence NMR spectroscopy and protein-protein binding mapping

    PMID:24810720

    Open questions at the time
    • Conformational states upon binding not resolved
    • Functional consequence of competitive partner binding untested
  14. 2014 High

    In vivo knockout studies placed the ATF7IP-MBD1-SETDB1 axis in Aire-dependent thymic tolerance and X-inactivation maintenance, demonstrating MBD1's role in organismal epigenetic silencing programs.

    Evidence Co-IP, Mbd1 knockout mouse phenotyping and thymic transcriptomics, Xi-linked reporter reactivation with pathway-specific knockdowns

    PMID:24464130 PMID:25028596

    Open questions at the time
    • Direct chromatin targets at Xi and TSA loci incompletely mapped
    • Whether the same complex operates at both contexts is not directly compared
  15. 2013 Medium

    Cancer-context studies linked MBD1 to EMT and antioxidant control by forming repressive complexes (Twist/SIRT1 at CDH1; c-Myc at KEAP1) at specific promoters.

    Evidence Co-IP, ChIP, reporter assays, gain/loss-of-function in cancer cells

    PMID:23331011 PMID:26980696

    Open questions at the time
    • Single-lab studies without reciprocal validation across systems
    • Direct vs indirect promoter occupancy not always resolved
  16. 2017 High

    Demonstrating opposite domain-specific effects on TET1 — MBD inhibiting and CXXC3 promoting 5mC oxidation — recast MBD1 as an active modulator of DNA demethylation at heterochromatin rather than a passive reader.

    Evidence Live-cell imaging, 5hmC flow cytometry, ChIP, domain-deletion mutants; optochemical TET1 kinetics with domain mutants

    PMID:28449087 PMID:35709470

    Open questions at the time
    • In vivo balance between the two isoforms genome-wide unknown
    • Physiological loci where TET1 modulation matters not defined
  17. 2018 High

    Linking MBD1 to DNMT3a recruitment at Oprm1/Kcna2 and later to SUV39H1-driven H3K9me3 silencing established MBD1 as a driver of injury-induced gene silencing underlying neuropathic pain.

    Evidence ChIP, MBD1 knockout mice, DRG-specific viral overexpression/rescue, behavioral pain assays, western blot

    PMID:30266739 PMID:41090695

    Open questions at the time
    • How MBD1 is recruited after nerve injury not fully mechanistic
    • Relative contributions of DNMT3a vs SUV39H1 arms not dissected
  18. 2013 Medium

    Finding MBD1 at DNA damage sites bound to MDC1 and required for checkpoint activation extended its function into the DNA damage response.

    Evidence Co-IP, siRNA knockdown, gamma-H2AX assays, clonogenic survival

    PMID:23588667

    Open questions at the time
    • Single Co-IP without reciprocal validation of MDC1 interaction
    • Whether recruitment depends on chromatin reading is unclear
  19. 2023 High

    Identifying MBD1 as a PARP1-recruiting factor that stabilizes stalled replication forks and limits transcription-replication conflicts defined a non-transcriptional genome-maintenance role.

    Evidence iPOND/PLA-EdU, R-loop detection, DNA fiber assays, siRNA depletion, PARP1 Co-IP

    PMID:37949945

    Open questions at the time
    • How MBD1 selects stalled forks mechanistically unknown
    • Relationship to its transcriptional silencing functions not integrated
  20. 2024 Medium

    Single-molecule kinetics showed the MBD prefers tandem symmetric methyl-CpG and DNA forks, offering a model for epigenetic boundary maintenance.

    Evidence SiMKEPS single-molecule rate-constant measurements (preprint) on varied CpG/structural substrates

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • In vitro kinetics not validated against in vivo occupancy
  21. 2025 Medium

    Characterizing an MDS-associated long isoform that switches MBD1 from methylated to unmethylated CpG binding linked aberrant splicing of MBD1 to a hematopoietic differentiation disease phenotype via BCOR.

    Evidence Isoform overexpression in human HSPCs, ChIP/ATAC-seq, antisense depletion, differentiation assays (preprint)

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Causal role of MBD1-L in patient disease not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MBD1's distinct functional modes — methylation-dependent silencing, methylation-independent CXXC3 targeting, TET1 modulation, and replication-fork protection — are coordinated within a cell and across the cell cycle remains unresolved.
  • No integrated model linking transcriptional and replication-fork roles
  • Genome-wide isoform- and modification-state-resolved occupancy lacking
  • Structure of full-length MBD1 or its native complexes undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 5 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-4839726 Chromatin organization 4 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2
Partners
CAF-1 P150HDAC3HP1MCAF1PARP1PIAS1SETDB1SUV39H1
Complex memberships
CAF-1/MBD1/SETDB1HDAC3-MBD1MBD1·MCAF1(ATF7IP)·SETDB1MBD1·Suv39h1·HP1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Solution structure of the MBD of human MBD1 bound to methylated DNA was determined by NMR. DNA binding causes a loop in MBD1 to fold into a novel DNA binding interface; recognition of methyl groups and CG sequence is mediated by five highly conserved residues forming a hydrophobic patch (including Asp32, Tyr34, Arg44). Multi-dimensional heteronuclear NMR spectroscopy with site-directed mutagenesis Cell High 11371345
1999 Solution structure of the free MBD of human MBD1 determined by NMR; it folds into an alpha/beta-sandwich with a large positively charged surface identified as the DNA interaction site. Conserved residues Tyr34, Asp32, and three basic residues are critical for DNA binding, established by site-directed mutagenesis and chemical shift mapping. Multi-dimensional heteronuclear NMR spectroscopy with site-directed mutagenesis The EMBO journal High 10581239
1999 MBD1 possesses isoforms (v1/v2 with CXXC1-3; v3/v4 with CXXC1-2) due to alternative splicing. The CXXC3 domain in isoforms v1/v2 confers binding to unmethylated DNA and transcriptional repression of unmethylated promoters, whereas the MBD confers methylation-dependent repression. Both the MBD and CXXC domains, plus the C-terminal TRD, cooperate for transcriptional regulation. Transfection of GFP-fused isoforms in methylation-deficient Drosophila SL2 and mammalian CHO-K1 cells; reporter assays; EMSA with bacterially expressed domains Molecular and cellular biology High 10454587 10866667
2000 MBD1 contains a powerful C-terminal transcriptional repression domain (TRD) that actively represses transcription at a distance. Methylation-dependent repression in vivo requires both the TRD and the MBD. Repression is sensitive to trichostatin A (HDAC inhibitor), indicating dependence on histone deacetylation. Endogenous MBD1 concentrates at centromeric heterochromatin where acetylated H4 is deficient. MBD1 is not a component of the MeCP1 complex. Transient transfection reporter assays; trichostatin A treatment; immunofluorescence localization; co-immunoprecipitation (negative for MeCP1) Molecular and cellular biology High 10648624
2003 MBD1 directly interacts with histone H3 methylase Suv39h1 and methyl-lysine binding protein HP1 via its MBD in vitro and in cells. Suv39h1 enhances MBD1-mediated transcriptional repression through the MBD (not the TRD). MBD1 links to HDACs through Suv39h1, resulting in coupled H3K9 methylation and histone deacetylation for gene inactivation. In vitro GST pulldown; co-immunoprecipitation; reporter gene assays The Journal of biological chemistry High 12711603
2003 MBD1 interacts with the p150 subunit of chromatin assembly factor 1 (CAF-1), forming a multiprotein complex that also contains HP1alpha. The interaction requires the MBD of MBD1 and maps to the C-terminus of CAF-1 p150. Overexpression of the CAF-1 p150 C-terminus displaces MBD1 from heterochromatic foci without disrupting global heterochromatin structure. Co-immunoprecipitation; immunofluorescence colocalization; dominant-negative overexpression Molecular and cellular biology High 12697822
2003 A mediator protein MCAF (MBD1-containing chromatin-associated factor) interacts with the TRD of MBD1, identified by yeast two-hybrid. MCAF interacts with both MBD1 and the transcription factor Sp1. The MBD1-MCAF complex blocks transcription through Sp1 on methylated promoters via a histone deacetylation-resistant mechanism. Yeast two-hybrid; co-immunoprecipitation; reporter gene assays Molecular and cellular biology High 12665582
2004 MBD1 forms a stable complex with histone H3K9 methylase SETDB1. During S phase, MBD1 recruits SETDB1 to the CAF-1 p150 subunit to form an S phase-specific CAF-1/MBD1/SETDB1 complex that facilitates H3K9 methylation during replication-coupled chromatin assembly. Absence of MBD1 causes loss of H3K9 methylation at multiple genomic loci and derepression of p53BP2. Co-immunoprecipitation; ChIP; siRNA knockdown; cell fractionation during S phase Molecular cell High 15327775
2004 Mouse Mbd1 isoform Mbd1a contains a CXXC3 domain that binds specifically to nonmethylated CpG sites in vivo and in vitro, explaining methylation-independent heterochromatin localization. CXXC3-mediated targeting is responsible for repression of nonmethylated reporter genes, while MBD-mediated binding is required for repression of methylated reporters. Transfection studies with domain mutants; DNA binding assays; fluorescence microscopy in methylation-deficient mouse cells Molecular and cellular biology High 15060159
2005 MCAF1 (ATF7ip/AM) is required for transcriptional repression and heterochromatin formation by MBD1, together with SETDB1. Both MCAF1 and a newly identified MCAF2 interact with MBD1, SETDB1, and Sp1 via two conserved distinct domains. An MBD1 mutant lacking MCAF interaction perturbs HP1-enriched heterochromatin formation, establishing the MBD1·MCAF1·SETDB1 complex as required for heterochromatic domain formation. Co-immunoprecipitation; in vitro binding; siRNA knockdown; immunofluorescence; reporter assays The Journal of biological chemistry High 15691849
2005 The intracellular domain of teneurin-1 interacts with MBD1 and co-localizes with it in nuclear matrix-associated foci, identified by yeast two-hybrid and validated by co-transfection and co-localization studies. Yeast two-hybrid; co-transfection; co-localization immunofluorescence; nuclear fractionation Experimental cell research Medium 15777793
2006 MBD1 is SUMOylated at two conserved C-terminal lysine residues by PIAS1 and PIAS3 E3 SUMO ligases. Sumoylated MBD1 can still bind methylated DNA but fails to form a complex with SETDB1 and cannot efficiently repress target gene p53BP2, indicating that SUMO conjugation antagonizes formation of the repressive MBD1-SETDB1 complex. In vivo sumoylation assay; co-immunoprecipitation; reporter gene assay; site-directed mutagenesis of SUMO acceptor lysines The EMBO journal High 17066076
2006 SUMOs (SUMO-2/3 and SUMO-1) directly interact with MCAF1. SUMOylation of MBD1 facilitates the interaction between MBD1 and MCAF1. Knockdown of SUMO-2/3 or SUMO-1 causes dissociation of MCAF1, trimethyl-H3K9, and HP1 proteins from MBD1-containing heterochromatin foci, demonstrating that SUMOs are required for heterochromatin assembly at MBD1 loci. Co-immunoprecipitation; siRNA knockdown; immunofluorescence The Journal of biological chemistry Medium 16757475
2006 PML-RARalpha recruits MBD1 to its target promoter through an HDAC3-mediated mechanism. Knockdown of HDAC3 alleviates PML-RAR-induced promoter silencing. Dominant-negative MBD1 mutants in hematopoietic precursors compromise PML-RARalpha's ability to block differentiation, demonstrating that an HDAC3-MBD1 complex is required for PML-RARalpha-mediated transcriptional repression and transformation. ChIP; siRNA knockdown; retroviral expression of dominant-negative MBD1; differentiation assays Proceedings of the National Academy of Sciences of the United States of America High 16432238
2007 MBD1 interacts with PcG proteins Ring1b and hPc2 (components of Polycomb repressive complex 1) via its CXXC domains (Ring1b) and the chromodomain of hPc2. Both MBD1 and hPc2 are present at silenced HOXA gene loci; knockdown of either derepresses HOXA genes. An MBD1 mutant lacking CXXC domains loses co-localization with PcG proteins in heterochromatin foci. Co-immunoprecipitation; ChIP; siRNA knockdown; immunofluorescence with domain mutants; 5-azadeoxycytidine treatment The Journal of biological chemistry High 17428788
2008 Mbd1 binds to the Fgf-2 promoter in adult neural stem/progenitor cells (NSPCs) and represses its expression via a DNA methylation-dependent mechanism. In Mbd1-deficient NSPCs, the Fgf-2 promoter is hypomethylated and Fgf-2 is upregulated, leading to impaired neuronal differentiation. Acute knockdown of Mbd1 or overexpression of Fgf-2 both inhibit neuronal differentiation. ChIP; bisulfite sequencing; DNA methylation inhibitor treatment; siRNA knockdown; overexpression in adult NSPCs The Journal of biological chemistry High 18689796
2010 MBD1 directly represses miR-184 expression in adult neural stem/progenitor cells. MBD1 deficiency leads to elevated miR-184, which promotes proliferation and inhibits differentiation. miR-184 targets the 3'-UTR of Numblike (Numbl) mRNA to suppress its translation. Expression of exogenous Numbl rescues the aNSC defects from miR-184 overexpression or MBD1 deficiency, establishing a MBD1→miR-184→Numbl regulatory axis. ChIP; luciferase 3'-UTR reporter assay; miRNA overexpression/inhibition; rescue experiments in aNSCs Cell stem cell High 20452318
2010 The MBD domain of MBD1 binds methylated DNA with sequence-context preference and is necessary and sufficient for recruitment of MBD1 to specific genomic loci in human cells. CXXC3 DNA binding is largely dispensable for in vivo targeting to methylated target genes. ChIP; in vitro DNA binding assays with purified domains; MBD domain point mutants Nucleic acids research High 20378711
2013 MBD1 and Sp1-binding MCAF1 form a ternary complex; MCAF1 interacts with MBD1 via its TRD and with Sp1 separately. The MBD1-MCAF complex blocks Sp1-mediated transcription at methylated promoters. Co-immunoprecipitation; in vitro binding; reporter gene assays; MCAF1 knockdown rescue PloS one Medium 23349673
2013 MBD1 forms a complex with Twist and SIRT1 on the CDH1 (E-cadherin) promoter, resulting in reduced E-cadherin transcription and promotion of epithelial-mesenchymal transition in pancreatic cancer cells. Co-immunoprecipitation; ChIP; reporter assays; gain/loss-of-function Current molecular medicine Medium 23331011
2013 MBD1 is recruited to DNA damage sites and binds MDC1 (mediator of DNA damage checkpoint protein 1). MBD1 knockdown impairs DNA damage checkpoint activation and reduces DNA repair capacity, sensitizing cells to radiation and cisplatin. Co-immunoprecipitation; siRNA knockdown; DNA damage assays (gamma-H2AX); clonogenic survival assay International journal of oncology Medium 23588667
2014 The transcriptional regulator Aire interacts with ATF7ip (MCAF1) and MBD1. Mbd1-knockout mice develop autoimmunity with a defect in Aire-dependent thymic expression of tissue-specific antigens, demonstrating that the ATF7ip-MBD1 complex is required for Aire's targeting of TSA loci. Co-immunoprecipitation; Mbd1 knockout mouse phenotyping; transcriptome analysis of thymic epithelial cells Nature immunology High 24464130
2014 ATF7IP-MBD1-SETDB1 pathway contributes to X chromosome inactivation maintenance. siRNA-mediated knockdown of Mbd1 or Setdb1, but not unrelated H3K9 methyltransferases, induces activation of silenced Xi-linked reporter genes in mouse embryonic fibroblasts, demonstrating functional specificity within the ATF7IP-MBD1-SETDB1 axis. siRNA knockdown; Xi-linked reporter gene reactivation assay; combined inhibition of multiple Xi maintenance pathways Epigenetics & chromatin High 25028596
2014 The C-terminal transcriptional repressor domain (TRD) of MBD1 (residues A529–P592) is intrinsically disordered. Despite lacking tertiary structure, it binds selectively to different partners: MPG and MCAF1 bind both N- and C-terminal residues of the TRD, whereas HDAC3 preferentially binds only the C-terminal region. NMR spectroscopy; protein-protein binding assays Scientific reports High 24810720
2016 MBD1 epigenetically silences KEAP1 in pancreatic cancer cells, and c-Myc is an MBD1 interaction partner in this silencing. MBD1 knockdown decreases antioxidant response and ARE-target gene expression through upregulation of KEAP1. Co-immunoprecipitation; ChIP; dual-luciferase reporter assay; siRNA knockdown Current molecular medicine Medium 26980696
2017 Mbd1 interacts with and enhances Tet1-mediated 5mC oxidation to 5hmC specifically at heterochromatic DNA in mammalian cells, dependent on the CXXC3 domain of Mbd1. The MBD-only isoform (lacking CXXC3) blocks Tet1-mediated 5mC oxidation, showing opposite effects of the two isoforms. Tet1 catalytic activity ultimately leads to displacement of Mbd1 from methylated DNA. Live-cell fluorescence imaging; flow cytometry for 5hmC; ChIP; overexpression of domain deletion mutants Nucleic acids research High 28449087
2018 MBD1 represses Oprm1 (mu-opioid receptor) and Kcna2 gene expression in DRG neurons by recruiting DNA methyltransferase DNMT3a to their promoters. MBD1-deficient mice show reduced responses to acute noxious stimuli and blunted neuropathic pain; DRG-specific MBD1 overexpression restores these phenotypes. ChIP; MBD1 knockout mouse; DRG-specific overexpression via viral vector; behavioral pain assays The Journal of neuroscience High 30266739
2022 MBD1 directly inhibits TET1-catalyzed 5mC oxidation kinetics via its MBD domain (which competes for mCpG binding), while the CXXC3 domain of MBD1 promotes TET1 oxidation kinetics by binding the unmethylated CpG product. The transcriptional repressor domain of MBD1 does not affect TET1 regulation, demonstrating distinct domain-specific contributions. Optochemical control of TET1 with photocaged serine; in vivo 5mC oxidation kinetics; MBD1 domain mutants ACS chemical biology High 35709470
2022 MBD1 directly represses miR-5701 expression together with HDAC3 by forming a complex that binds the miR-5701 promoter, which in turn regulates FGFR2 in gastric cancer cells. ChIP; co-immunoprecipitation; siRNA knockdown; luciferase reporter assay Aging Medium 35876658
2023 MBD1 is essential for replication fork stability by recruiting PARP1 to stalled replication forks. Loss of MBD1 causes dissociation of PARP1 from forks, increased transcription-replication conflicts (T-R conflicts), elevated R-loops, accelerated fork progression, and DNA2-dependent degradation of stalled forks. Proximity ligation assay combined with EdU (iPOND); R-loop detection; DNA fiber assay; siRNA depletion; PARP1 co-immunoprecipitation Cancer gene therapy High 37949945
2024 The MBD of human MBD1 binds preferentially to tandem (consecutive) symmetrically methylated CpG sites and DNA forks, with defined binding and dissociation rate constants measured at single-molecule level. This provides a mechanistic model for epigenetic boundary maintenance. Single-molecule kinetics (SiMKEPS) measuring rate constants on DNA substrates with varying CpG patterns and structural motifs bioRxivpreprint Medium
2025 MBD1 is recruited to the Oprm1 promoter following peripheral nerve injury and recruits SUV39H1 to drive H3K9me3-mediated transcriptional silencing of Oprm1 in DRG neurons. Genetic ablation of MBD1 reversed injury-induced MOR downregulation, attenuated H3K9me3 enrichment at the Oprm1 promoter, and alleviated neuropathic pain despite persistent SUV39H1 upregulation. ChIP; MBD1 genetic knockout mouse; behavioral pain assays; western blot Molecular pain High 41090695
2025 An MDS-associated long isoform of MBD1 (MBD1-L) arising from aberrant splicing switches MBD1's binding behavior from methylated to unmethylated CpGs, redirecting its heterochromatin-promoting activity and causing broad downregulation of CpG-rich promoters. MBD1-L overexpression in healthy HSPCs recapitulates MDS erythroid differentiation defects. Secondary epigenetic effects are mediated via downstream target BCOR. Isoform overexpression in human HSPCs; ChIP/ATAC-seq; antisense oligonucleotide depletion; differentiation assays bioRxivpreprint Medium

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Molecular cell 353 15327775
2010 Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell stem cell 263 20452318
2001 Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell 252 11371345
2003 Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. The Journal of biological chemistry 209 12711603
2000 Active repression of methylated genes by the chromosomal protein MBD1. Molecular and cellular biology 208 10648624
1999 Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein MBD1 isoforms. Molecular and cellular biology 165 10454587
2004 Mbd1 is recruited to both methylated and nonmethylated CpGs via distinct DNA binding domains. Molecular and cellular biology 139 15060159
2000 Mechanism of transcriptional regulation by methyl-CpG binding protein MBD1. Molecular and cellular biology 138 10866667
2006 Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain. Molecular pharmacology 134 16670375
2005 Transcriptional repression and heterochromatin formation by MBD1 and MCAF/AM family proteins. The Journal of biological chemistry 107 15691849
1999 Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1. The EMBO journal 100 10581239
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
2006 The methyl-CpG binding protein MBD1 is required for PML-RARalpha function. Proceedings of the National Academy of Sciences of the United States of America 84 16432238
2008 Epigenetic regulation of the stem cell mitogen Fgf-2 by Mbd1 in adult neural stem/progenitor cells. The Journal of biological chemistry 82 18689796
2006 Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation. The Journal of biological chemistry 79 16757475
2003 The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1. Molecular and cellular biology 78 12697822
2003 MCAF mediates MBD1-dependent transcriptional repression. Molecular and cellular biology 77 12665582
2014 The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance. Nature immunology 73 24464130
2014 The Mbd1-Atf7ip-Setdb1 pathway contributes to the maintenance of X chromosome inactivation. Epigenetics & chromatin 71 25028596
2010 Recruitment of MBD1 to target genes requires sequence-specific interaction of the MBD domain with methylated DNA. Nucleic acids research 70 20378711
2005 The intracellular domain of teneurin-1 interacts with MBD1 and CAP/ponsin resulting in subcellular codistribution and translocation to the nuclear matrix. Experimental cell research 57 15777793
2018 MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 30266739
2013 An epigenetic feedback regulatory loop involving microRNA-195 and MBD1 governs neural stem cell differentiation. PloS one 50 23349673
2013 Up-regulation of MBD1 promotes pancreatic cancer cell epithelial-mesenchymal transition and invasion by epigenetic down-regulation of E-cadherin. Current molecular medicine 49 23331011
2008 Enhanced expression of murine beta-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice. Virology 48 18752820
2006 Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins. The EMBO journal 48 17066076
2015 An epigenetic regulator: methyl-CpG-binding domain protein 1 (MBD1). International journal of molecular sciences 40 25751725
2007 Overlapping roles of the methylated DNA-binding protein MBD1 and polycomb group proteins in transcriptional repression of HOXA genes and heterochromatin foci formation. The Journal of biological chemistry 33 17428788
2003 Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2. Biochemical and biophysical research communications 33 12646234
2009 RNA interference of MBD1 in BxPC-3 human pancreatic cancer cells delivered by PLGA-poloxamer nanoparticles. Cancer biology & therapy 32 19276660
2017 Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 28100736
2017 Methyl-CpG binding domain protein 1 regulates localization and activity of Tet1 in a CXXC3 domain-dependent manner. Nucleic acids research 27 28449087
2003 MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers. Oncogene 27 12776203
2013 Silencing of MBD1 reverses pancreatic cancer therapy resistance through inhibition of DNA damage repair. International journal of oncology 26 23588667
2001 Regulation of transcription and chromatin by methyl-CpG binding protein MBD1. Brain & development 23 11738867
2020 NR2F2-AS1 accelerates cell proliferation through regulating miR-4429/MBD1 axis in cervical cancer. Bioscience reports 18 32469064
2016 MBD1 is an Epigenetic Regulator of KEAP1 in Pancreatic Cancer. Current molecular medicine 16 26980696
2008 Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference. BMC cancer 15 18445260
2014 Construction of eukaryotic expression vector with mBD1-mBD3 fusion genes and exploring its activity against influenza A virus. Viruses 13 24632574
2014 Transcriptional repressor domain of MBD1 is intrinsically disordered and interacts with its binding partners in a selective manner. Scientific reports 12 24810720
2019 MBD1 promotes the malignant behavior of gallbladder cancer cells and induces chemotherapeutic resistance to gemcitabine. Cancer cell international 9 31516389
2015 Molecular dynamics study of the recognition of dimethylated CpG sites by MBD1 protein. Journal of chemical information and modeling 9 25658035
2022 MBD1/HDAC3-miR-5701-FGFR2 axis promotes the development of gastric cancer. Aging 7 35876658
2023 LncRNA SNHG20 silencing inhibits hepatocellular carcinoma progression by sponging miR-5095 from MBD1. American journal of translational research 5 37434830
2022 Optochemical Control of TET Dioxygenases Enables Kinetic Insights into the Domain-Dependent Interplay of TET1 and MBD1 while Oxidizing and Reading 5-Methylcytosine. ACS chemical biology 4 35709470
2022 Forward genetic screen of homeostatic antibody levels in the Collaborative Cross identifies MBD1 as a novel regulator of B cell homeostasis. PLoS genetics 4 36574452
2012 A semi-quantitative assay of overall DNA methylation status using Methyl-CpG binding protein (MBD1). BMC research notes 4 22583687
2008 [Activation of multiple tumor suppressor genes by MBD1 siRNA in pancreatic cancer cell line BxPC-3]. Zhonghua yi xue za zhi 3 19062732
2023 MBD1 protects replication fork stability by recruiting PARP1 and controlling transcription-replication conflicts. Cancer gene therapy 2 37949945
2025 MBD1-dependent recruitment of SUV39h1 induces H3K9me3-mediated transcriptional silencing of Oprm1 in dorsal root ganglia after peripheral nerve injury. Molecular pain 0 41090695
2017 MBD1 and MeCP2 expression in embryos and placentas from transgenic cloned goats. Zygote (Cambridge, England) 0 28669357
2005 Effect of antisense MBD1 gene eukaryotic expression plasmid on expression of MBD1 gene in human biliary tract carcinoma cells. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 0 16696318

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