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. MBD4 may function to mediate the biological consequences of the methylation signal. In addition, MBD4 has protein sequence similarity to bacterial DNA repair enzymes and thus may have some function in DNA repair. Further, MBD4 gene mutations are detected in tumors with primary microsatellite-instability (MSI), a form of genomic instability associated with defective DNA mismatch repair, and MBD4 gene meets 4 of 5 criteria of a bona fide MIS target gene.
Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW et al. (1998). "A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer". Cancer Res.58 (22): 5248–57. PMID9823339.
Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A (1999). "Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes". Mamm. Genome10 (9): 906–12. doi:10.1007/s003359901112. PMID10441743.
Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A (1999). "The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites". Nature401 (6750): 301–4. doi:10.1038/45843. PMID10499592.
Riccio A, Aaltonen LA, Godwin AK, Loukola A, Percesepe A, Salovaara R et al. (1999). "The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability". Nat. Genet.23 (3): 266–8. doi:10.1038/15443. PMID10545939.
Petronzelli F, Riccio A, Markham GD, Seeholzer SH, Stoerker J, Genuardi M et al. (2000). "Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase". J. Biol. Chem.275 (42): 32422–9. doi:10.1074/jbc.M004535200. PMID10930409.
Yamada T, Koyama T, Ohwada S, Tago K, Sakamoto I, Yoshimura S et al. (2002). "Frameshift mutations in the MBD4/MED1 gene in primary gastric cancer with high-frequency microsatellite instability". Cancer Lett.181 (1): 115–20. doi:10.1016/S0304-3835(02)00043-5. PMID12430186.
Evertson S, Wallin A, Arbman G, Rütten S, Emterling A, Zhang H et al. (2003). "Microsatellite instability and MBD4 mutation in unselected colorectal cancer". Anticancer Res.23 (4): 3569–74. PMID12926109.
Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID14667819.
Zhang X, Krutchinsky A, Fukuda A, Chen W, Yamamura S, Chait BT et al. (2005). "MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription". Mol. Cell19 (1): 89–100. doi:10.1016/j.molcel.2005.05.015. PMID15989967.