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 these genes may function as a mediator of the biological consequences of the methylation signal. It is also reported that MBD2 and MBD3 recruit the NuRD complex to regions of DNA depending on their selective binding of methylated CpG sites. Therefore, MBD2/NuRD and MBD3/NuRD define two distinct protein complexes with different biochemical and functional properties.[3]
Interactions
Methyl-CpG-binding domain protein 2 has been shown to interact with:
↑ 4.04.14.2Brackertz M, Boeke J, Zhang R, Renkawitz R (October 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. PMID12183469.
↑ 6.06.1Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (September 1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. PMID10471499.
↑Jiang CL, Jin SG, Pfeifer GP (December 2004). "MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex". J. Biol. Chem. 279 (50): 52456–64. doi:10.1074/jbc.M409149200. PMID15456747.
↑Sekimata M, Takahashi A, Murakami-Sekimata A, Homma Y (November 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. PMID11553631.
↑Boeke J, Ammerpohl O, Kegel S, Moehren U, Renkawitz R (November 2000). "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. PMID10950960.
Further reading
Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ (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. PMID9610721.
Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D (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. PMID9790534.
Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. doi:10.1038/27699. PMID9804427.
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. PMID10050851.
Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. PMID10471499.
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. PMID10947852.
Boeke J, Ammerpohl O, Kegel S, Moehren U, Renkawitz R (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. PMID10950960.
Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y, Howard BH (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. PMID11102443.
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. PMID11553631.
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. PMID11960994.
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. PMID12124384.
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. PMID12177048.
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. PMID12183469.