MBD3 Background Information
Methylation of DNA contributes to the regulation of gene transcription in both mammalian and invertebrate systems (1). DNA methylation predominates on cytosine residues that are present in dinucleotide motifs consisting of a 5’ cytosine followed by guanosine (CpG), and it requires the enzymatic activity of DNA methyltransferase, which results in transcriptional repression of the methylated gene. Several proteins have been identified that associate with the methyl-CpG sites, and they include methyl-CpG binding protein-1 (MBD1), MBD2, MBD3, MBD4 and MeCP2 (3,4). Expression of the MBD proteins is highest in somatic tissues (5). MBD1 binds in a context specific manner to methyl-CpG rich domains and, in turn, mediates the transcriptional inhibition that is commonly observed with DNA methylation (3). Similarly, MBD2 inhibits transcription of methylated genes by associating with histone deacetylase (HDAC1) within the MeCP1 repressor complex (6). In addition, MBD4, which is also designated MED1, associates with the mismatch repair protein MLH1 and preferentially binds to methylated cytosine residues in mismatched base pairs (7). MeCP2 binds tightly to chromosomes in a methylation-dependent manner and associates with a corepressor complex containing the transcriptional repressor mSin3A and histone deacetylases (2). MeCP2 binds tightly to chromosomes in a methylation-dependent manner and associates with a corepressor complex containing the transcriptional repressor mSin3A and histone deacetylases (2).
