Methyl-CpG-binding domain protein 2

Methyl-CpG binding domain protein 2
Identifiers
Symbols	MBD2; DKFZp586O0821; DMTase; NY-CO-41
External IDs	OMIM: 603547 MGI: 1333813 HomoloGene: 2918 GeneCards: MBD2 Gene
Gene Ontology Molecular function • DNA binding • chromatin binding • satellite DNA binding • mRNA binding • protein binding • methyl-CpG binding • methyl-CpG binding • protein domain specific binding • siRNA binding • C2H2 zinc finger domain binding Cellular component • histone deacetylase complex • heterochromatin • nucleus • nucleus • cytoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • positive regulation of Wnt receptor signaling pathway • regulation of cell proliferation • maternal behavior • cellular protein complex assembly • negative regulation of transcription, DNA-dependent Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8932	17191
Ensembl	ENSG00000134046	ENSMUSG00000024513
UniProt	Q9UBB5	Q9Z2E1
RefSeq (mRNA)	NM_003927.4	NM_010773.2
RefSeq (protein)	NP_003918.1	NP_034903.2
Location (UCSC)	Chr 18: 51.68 – 51.75 Mb	Chr 18: 70.73 – 70.79 Mb
PubMed search	[1]	[2]

Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the MBD2 gene.^[1][2]

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG-binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1, and MBD2 can also repress transcription from methylated gene promoters. The protein encoded by this gene may function as a mediator of the biological consequences of the methylation signal. It is also reported that this protein functions as a demethylase to activate transcription, as DNA methylation causes gene silencing.^[3]

Interactions

Methyl-CpG-binding domain protein 2 has been shown to interact with HDAC1,^[4][5][6] Histone deacetylase 2,^[4][5][6] SIN3A,^[7] MIZF,^[8] MBD3^[6][9] and GATAD2B.^[4][10]

References

1. ^ Hendrich B, Bird A (Nov 1998). "Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins". Mol Cell Biol 18 (11): 6538–47. PMC 109239. PMID 9774669. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109239. 
2. ^ Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A (Sep 1999). "Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes". Mamm Genome 10 (9): 906–12. doi:10.1007/s003359901112. PMID 10441743. 
3. ^ "Entrez Gene: MBD2 methyl-CpG binding domain protein 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8932. 
4. ^ ^{a b c} Brackertz, Marc; Boeke Joern, Zhang Ru, Renkawitz Rainer (Oct. 2002). "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3". J. Biol. Chem. (United States) 277 (43): 40958–66. doi:10.1074/jbc.M207467200. ISSN 0021-9258. PMID 12183469. 
5. ^ ^{a b} Ng, H H; Zhang Y, Hendrich B, Johnson C A, Turner B M, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (Sep. 1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. (UNITED STATES) 23 (1): 58–61. doi:10.1038/12659. ISSN 1061-4036. PMID 10471499. 
6. ^ ^{a b c} Zhang, Y; Ng H H, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (Aug. 1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. (UNITED STATES) 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. ISSN 0890-9369. PMC 316920. PMID 10444591. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316920. 
7. ^ Boeke, J; Ammerpohl O, Kegel S, Moehren U, Renkawitz R (Nov. 2000). "The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A". J. Biol. Chem. (UNITED STATES) 275 (45): 34963–7. doi:10.1074/jbc.M005929200. ISSN 0021-9258. PMID 10950960. 
8. ^ Sekimata, M; Takahashi A, Murakami-Sekimata A, Homma Y (Nov. 2001). "Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2". J. Biol. Chem. (United States) 276 (46): 42632–8. doi:10.1074/jbc.M107048200. ISSN 0021-9258. PMID 11553631. 
9. ^ Jiang, Chun-Ling; Jin Seung-Gi, Pfeifer Gerd P (Dec. 2004). "MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex". J. Biol. Chem. (United States) 279 (50): 52456–64. doi:10.1074/jbc.M409149200. ISSN 0021-9258. PMID 15456747. 
10. ^ Feng, Qin; Cao Ru, Xia Li, Erdjument-Bromage Hediye, Tempst Paul, Zhang Yi (Jan. 2002). "Identification and Functional Characterization of the p66/p68 Components of the MeCP1 Complex". Mol. Cell. Biol. (United States) 22 (2): 536–46. doi:10.1128/MCB.22.2.536-546.2002. ISSN 0270-7306. PMC 139742. PMID 11756549. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139742. 

Further reading

• Scanlan MJ, Chen YT, Williamson B, et al. (1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". Int. J. Cancer 76 (5): 652–8. doi:10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P. PMID 9610721. 
• Zhang Y, LeRoy G, Seelig HP, et al. (1998). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell 95 (2): 279–89. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534. 
• Tong JK, Hassig CA, Schnitzler GR, et al. (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature 395 (6705): 917–21. doi:10.1038/27699. PMID 9804427. 
• Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M (1999). "A mammalian protein with specific demethylase activity for mCpG DNA". Nature 397 (6720): 579–83. doi:10.1038/17533. PMID 10050851. 
• Zhang Y, Ng HH, Erdjument-Bromage H, et al. (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316920. 
• Ng HH, Zhang Y, Hendrich B, et al. (1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. PMID 10471499. 
• Tatematsu KI, Yamazaki T, Ishikawa F (2000). "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase". Genes Cells 5 (8): 677–88. doi:10.1046/j.1365-2443.2000.00359.x. PMID 10947852. 
• Boeke J, Ammerpohl O, Kegel S, et al. (2001). "The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A". J. Biol. Chem. 275 (45): 34963–7. doi:10.1074/jbc.M005929200. PMID 10950960. 
• Humphrey GW, Wang Y, Russanova VR, et al. (2001). "Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1". J. Biol. Chem. 276 (9): 6817–24. doi:10.1074/jbc.M007372200. PMID 11102443. 
• Feng Q, Zhang Y (2001). "The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes". Genes Dev. 15 (7): 827–32. doi:10.1101/gad.876201. PMC 312663. PMID 11297506. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=312663. 
• Sekimata M, Takahashi A, Murakami-Sekimata A, Homma Y (2001). "Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2". J. Biol. Chem. 276 (46): 42632–8. doi:10.1074/jbc.M107048200. PMID 11553631. 
• Müller-Tidow C, Kügler K, Diederichs S, et al. (2001). "Loss of expression of HDAC-recruiting methyl-CpG-binding domain proteins in human cancer". Br. J. Cancer 85 (8): 1168–74. doi:10.1054/bjoc.2001.2041. PMC 2375156. PMID 11710831. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2375156. 
• Feng Q, Cao R, Xia L, et al. (2002). "Identification and Functional Characterization of the p66/p68 Components of the MeCP1 Complex". Mol. Cell. Biol. 22 (2): 536–46. doi:10.1128/MCB.22.2.536-546.2002. PMC 139742. PMID 11756549. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139742. 
• Bakker J, Lin X, Nelson WG (2002). "Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells". J. Biol. Chem. 277 (25): 22573–80. doi:10.1074/jbc.M203009200. PMID 11960994. 
• Saito M, Ishikawa F (2002). "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". J. Biol. Chem. 277 (38): 35434–9. doi:10.1074/jbc.M203455200. PMID 12124384. 
• Detich N, Theberge J, Szyf M (2002). "Promoter-specific activation and demethylation by MBD2/demethylase". J. Biol. Chem. 277 (39): 35791–4. doi:10.1074/jbc.C200408200. PMID 12177048. 
• Brackertz M, Boeke J, Zhang R, Renkawitz R (2002). "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3". J. Biol. Chem. 277 (43): 40958–66. doi:10.1074/jbc.M207467200. PMID 12183469. 
• Krithivas A, Fujimuro M, Weidner M, et al. (2002). "Protein Interactions Targeting the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus to Cell Chromosomes". J. Virol. 76 (22): 11596–604. doi:10.1128/JVI.76.22.11596-11604.2002. PMC 136775. PMID 12388720. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=136775.