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). 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.