Gene Symbol: Mbd4
Description: methyl-CpG binding domain protein 4
Alias: Med1, methyl-CpG-binding domain protein 4, methyl-CpG-binding protein MBD4, mismatch-specific DNA N-glycosylase
Species: mouse
Products:     Mbd4

Top Publications

  1. Flajollet S, Lefebvre B, Rachez C, Lefebvre P. Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation. J Biol Chem. 2006;281:20338-48 pubmed
    ..Unexpectedly, Med1/TRAP220/DRIP205-depleted cells exhibited an exacerbated response to retinoids, both in terms transcriptional ..
  2. Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A. Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes. Mamm Genome. 1999;10:906-12 pubmed
    ..MeCP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of mammalian, nuclear proteins related by the presence in each of an amino acid motif called the ..
  3. Hajkova P, Jeffries S, Lee C, Miller N, Jackson S, Surani M. Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway. Science. 2010;329:78-82 pubmed publisher
    ..We demonstrate that DNA repair through BER represents a core component of genome-wide DNA demethylation in vivo and provides a mechanistic link to the extensive chromatin remodeling in developing PGCs. ..
  4. Wong E, Yang K, Kuraguchi M, Werling U, Avdievich E, Fan K, et al. Mbd4 inactivation increases Cright-arrowT transition mutations and promotes gastrointestinal tumor formation. Proc Natl Acad Sci U S A. 2002;99:14937-42 pubmed
    b>Mbd4 (methyl-CpG binding domain 4) is a novel mammalian repair enzyme that has been implicated biochemically in the repair of mismatched G-T residues at methylated CpG sites...
  5. Hendrich B, Hardeland U, Ng H, Jiricny J, Bird A. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature. 1999;401:301-4 pubmed
    ..Here we show that MBD4, an unrelated mammalian protein that contains a methyl-CpG binding domain, can also efficiently remove thymine or ..
  6. Millar C, Guy J, Sansom O, Selfridge J, MacDougall E, Hendrich B, et al. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science. 2002;297:403-5 pubmed
    The mammalian protein MBD4 contains a methyl-CpG binding domain and can enzymatically remove thymine (T) or uracil (U) from a mismatched CpG site in vitro...
  7. Wu P, Qiu C, Sohail A, Zhang X, Bhagwat A, Cheng X. Mismatch repair in methylated DNA. Structure and activity of the mismatch-specific thymine glycosylase domain of methyl-CpG-binding protein MBD4. J Biol Chem. 2003;278:5285-91 pubmed
    b>MBD4 is a member of the methyl-CpG-binding protein family. It contains two DNA binding domains, an amino-proximal methyl-CpG binding domain (MBD) and a C-terminal mismatch-specific glycosylase domain...
  8. Bardwell P, Martin A, Wong E, Li Z, Edelmann W, Scharff M. Cutting edge: the G-U mismatch glycosylase methyl-CpG binding domain 4 is dispensable for somatic hypermutation and class switch recombination. J Immunol. 2003;170:1620-4 pubmed
    ..However, G-T and G-U mismatches are also substrates of the methyl-CpG binding domain 4 (Mbd4) glycosylase...
  9. Cortellino S, Turner D, Masciullo V, Schepis F, Albino D, Daniel R, et al. The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity. Proc Natl Acad Sci U S A. 2003;100:15071-6 pubmed
    ..MMR also modulates sensitivity to other antitumor drugs. The base excision repair (BER) enzyme MED1 (also known as MBD4) interacts with the MMR protein MLH1...

More Information


  1. Clarke A, Sansom O. Analyzing tumor suppressor activities in the murine small intestine. Oncol Res. 2003;13:333-7 pubmed
    ..Finally, we have analyzed mice mutant for Mbd4 and show that this gene functions in vivo as a tumor suppressor.
  2. Meng H, Harrison D, Meehan R. MBD4 interacts with and recruits USP7 to heterochromatic foci. J Cell Biochem. 2015;116:476-85 pubmed publisher
    b>MBD4 is the only methyl-CpG binding protein that possesses a C-terminal glycosylase domain...
  3. Laub F, Aldabe R, Friedrich V, Ohnishi S, Yoshida T, Ramirez F. Developmental expression of mouse Krüppel-like transcription factor KLF7 suggests a potential role in neurogenesis. Dev Biol. 2001;233:305-18 pubmed
  4. Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998;18:6538-47 pubmed
    ..We describe here three novel human and mouse proteins (MBD2, MBD3, and MBD4) that contain the methyl-CpG binding domain. MBD2 and MBD4 bind specifically to methylated DNA in vitro...
  5. Mann W, Haaf T. Single cell RT-PCR on mouse embryos: a general approach for developmental biology. Methods Mol Biol. 2010;630:3-12 pubmed publisher
    ..It is tempting to speculate that cells expressing the reprogramming machinery have a higher developmental potential. ..
  6. Linke M, May A, Reifenberg K, Haaf T, Zechner U. The impact of ovarian stimulation on the expression of candidate reprogramming genes in mouse preimplantation embryos. Cytogenet Genome Res. 2013;139:71-9 pubmed publisher
    ..stimulation on the expression of developmentally important reprogramming genes (Apex1, Lig1, Lig3, Mbd2, Mbd3, Mbd4, and Polb) in single early mouse morula embryos (16-cell stage)...
  7. May A, Kirchner R, Muller H, Hartmann P, El Hajj N, Tresch A, et al. Multiplex rt-PCR expression analysis of developmentally important genes in individual mouse preimplantation embryos and blastomeres. Biol Reprod. 2009;80:194-202 pubmed publisher
    ..Immunolocalization of DNMT3A, MBD3, APEX1, and LIG3 in most or all nuclei of 40-60-cell embryos is a good indicator of functional activity of genes that are activated by the 16-cell stage...
  8. Hitoshi S, Ishino Y, Kumar A, Jasmine S, Tanaka K, Kondo T, et al. Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells. Nat Neurosci. 2011;14:957-64 pubmed publisher
    ..5-8.5 Gcm1(-/-); Gcm2(-/-) mice resulted in the impaired induction of neural stem cells. Our data suggest that Hes5 expression is serially activated first by Gcms and later by the canonical Notch pathway. ..
  9. Otani J, Arita K, Kato T, Kinoshita M, Kimura H, Suetake I, et al. Structural basis of the versatile DNA recognition ability of the methyl-CpG binding domain of methyl-CpG binding domain protein 4. J Biol Chem. 2013;288:6351-62 pubmed publisher
    The methyl-CpG binding domain (MBD) protein MBD4 participates in DNA repair as a glycosylase that excises mismatched thymine bases in CpG sites and also functions in transcriptional repression...
  10. Keil K, Altmann H, Mehta V, Abler L, Elton E, Vezina C. Catalog of mRNA expression patterns for DNA methylating and demethylating genes in developing mouse lower urinary tract. Gene Expr Patterns. 2013;13:413-24 pubmed publisher
    ..Future investigation into how DNA methylation patterns are established, maintained and remodeled during the course of embryonic prostatic bud formation may provide insight into prostate morphogenesis and disease. ..
  11. van der Zwaag B, Burbach J, Scharfe C, Oefner P, Brunner H, Padberg G, et al. Identifying new candidate genes for hereditary facial paresis on chromosome 3q21-q22 by RNA in situ hybridization in mouse. Genomics. 2005;86:55-67 pubmed
  12. Grigera F, Bellacosa A, Kenter A. Complex relationship between mismatch repair proteins and MBD4 during immunoglobulin class switch recombination. PLoS ONE. 2013;8:e78370 pubmed publisher
    ..b>Methyl CpG binding domain protein 4 (MBD4) binds to MutL homologue 1 (MLH1) and controls the post-transcriptional level of several MMR ..
  13. Yu A, Calvo J, Muthupalani S, Samson L. The Mbd4 DNA glycosylase protects mice from inflammation-driven colon cancer and tissue injury. Oncotarget. 2016;7:28624-36 pubmed publisher
    ..Here, we report that the Mbd4 DNA glycosylase is protective in the azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model of inflammation-..
  14. Hashimoto H, Zhang X, Cheng X. Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation. Nucleic Acids Res. 2012;40:8276-84 pubmed
    The mammalian DNA glycosylase--methyl-CpG binding domain protein 4 (MBD4)--is involved in active DNA demethylation via the base excision repair pathway. MBD4 contains an N-terminal MBD and a C-terminal DNA glycosylase domain...
  15. Ruddock D Cruz N, Xue J, Wilson K, Heffernan C, Prashadkumar S, Cooney M, et al. Dynamic changes in the localization of five members of the methyl binding domain (MBD) gene family during murine and bovine preimplantation embryo development. Mol Reprod Dev. 2008;75:48-59 pubmed
    ..Four MBD proteins (MeCP2 and MBDs 1-3) are linked to transcriptional repression and one (MBD4), to DNA repair...
  16. Boland M, Christman J. Characterization of Dnmt3b:thymine-DNA glycosylase interaction and stimulation of thymine glycosylase-mediated repair by DNA methyltransferase(s) and RNA. J Mol Biol. 2008;379:492-504 pubmed publisher
    ..G mismatch repair efficiency upon loss of DNA methyltransferase expression, as well as a requirement for an RNA component for correct T.G mismatch repair. ..
  17. Stumpf M, Waskow C, Krötschel M, van Essen D, Rodriguez P, Zhang X, et al. The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220. Proc Natl Acad Sci U S A. 2006;103:18504-9 pubmed
    The Mediator complex forms the bridge between transcriptional activators and RNA polymerase II. Mediator subunit Med1/TRAP220 is a key component of Mediator originally found to associate with nuclear hormone receptors...
  18. Sansom O, Bishop S, Bird A, Clarke A. MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR. Oncogene. 2004;23:5693-6 pubmed
    b>Mbd4 (methyl-binding domain 4) has been shown to be mutated in a high percentage of mismatch repair (MMR)-deficient colorectal tumours that exhibit microsatellite instability (MSI)...
  19. Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, et al. Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell. 2001;105:487-97 pubmed
    ..The structure indicates how MBD may access nucleosomal DNA without encountering steric interference from core histones, and provides a basis to interpret mutations linked to Rett syndrome in MeCP2. ..
  20. Ruzov A, Shorning B, Mortusewicz O, Dunican D, Leonhardt H, Meehan R. MBD4 and MLH1 are required for apoptotic induction in xDNMT1-depleted embryos. Development. 2009;136:2277-86 pubmed publisher
    ..b>MBD4 interacts directly with both DNMT1 and MLH1, leading to recruitment of the latter to heterochromatic sites that are ..
  21. Cortellino S, Wang C, Wang B, Bassi M, Caretti E, Champeval D, et al. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol. 2009;325:225-37 pubmed publisher
    ..We conclude that complex A and complex B factors play similar but distinct roles in ciliogenesis and Shh/Gli3 signaling. ..
  22. Sansom O, Zabkiewicz J, Bishop S, Guy J, Bird A, Clarke A. MBD4 deficiency reduces the apoptotic response to DNA-damaging agents in the murine small intestine. Oncogene. 2003;22:7130-6 pubmed
    b>MBD4 was originally identified through its methyl binding domain, but has more recently been characterized as a thymine DNA glycosylase that interacts with the mismatch repair (MMR) protein MLH1...
  23. Grigera F, Wuerffel R, Kenter A. MBD4 Facilitates Immunoglobulin Class Switch Recombination. Mol Cell Biol. 2017;37: pubmed publisher
    ..The BER enzyme methyl-CpG binding domain protein 4 (MBD4) has been linked to the MMR pathway through its interaction with MutL homologue 1 (MLH1)...