Scientific background: |
MBD4 (Methyl-CpG-Binding Domain Protein 4), also known as MED1, is a protein that in humans is encoded by the MBD4 gene. MBD4 specifically binds methylated DNA, colocalizes with methylated sequences, and is likely to mediate the effects of DNA methylation in mammalian cells (Hendrich and Bird, 1998). Riccio et al. (1999) mapped the MBD4 gene to chromosome 3q21-q22 by FISH. Hendrich and Bird (1998) found that both MBD2 and MBD4 specifically bound methylated DNA in vitro and colocalized with methylated sequences in vivo. They concluded that MBD2 and MBD4 are likely to be mediators of the effects of DNA methylation in mammalian cells. Hendrich et al. (1999) showed that MBD4 contains a methyl-CpG-binding domain that can efficiently remove thymine or uracil from mismatched CpG sites in vitro. Furthermore, the methyl-CpG-binding domain of MBD4 binds preferentially to 5-methylcytosine CpG-TpG mismatches--the primary product of deamination at methyl-CpG. |
References: |
1. 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. Mammalian Genome 10: 906-912, 1999.
2. Hendrich, B., Bird, A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Molec. Cell. Biol. 18: 6538-6547, 1998.
3. Riccio, A., Aaltonen, L. A., Godwin, A. K., Loukola, A., Percesepe, A., Salovaara, R., Masciullo, V., Genuardi M., Paravatou-Petsotas, M., Bassi, D. E., Ruggeri, B. A., Klein-Szanto, A. J. P., Testa, J. R., Neri, G., Bellacosa, A. The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability. (Letter) Nature Genet. 23: 266-268, 1999.
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