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First published online July 25, 2006
doi: 10.1242/10.1242/jcs.03099

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MBD family proteins: reading the epigenetic code

Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Science, 111 TW Alexander Drive, Mail Drop D4-04, Research Triangle Park, NC 27709, USA

View larger version (28K): [in a new window]   Fig. 1. Three-dimensional structure of an MBD domain. The diagram depicting key secondary structure elements was prepared using the program Ribbons with the structural coordinates for the rat MeCP2 MBD domain (Wakefield et al., 1999).

View larger version (11K): [in a new window]   Fig. 2. Characteristic domains of the methyl CpG binding (MBD) protein family. The predominant isoform of MeCP2 expressed in human brain has 498 residues. MBD1 has multiple isoforms, ranging in size from 50 to 70 kDa (605 residues, 586 residues, 556 residues, 549 residues and 503 residues). MBD2 contains 414 residues (44 kDa); MBD3 has two splice variants: 285 residues and 253 residues (27 and 32 kDa, respectively). MBD4 contains 554 residues (63 kDa). The MBD sequence motif is depicted as an orange box in each protein. Other defined sequence motifs in the individual MBD family members are also depicted.

View larger version (10K): [in a new window]   Fig. 3. Two potential models for gene regulation by MBD family members. (A) In the specific interaction model, each methylated locus is associated with one and only one MBD family member. In the example given, Gene A is associated only with MeCP2; Gene B is associated only with MBD2. (B) In the random interaction model, the association of a given methylated locus with an MBD family member is random. In the example given, Gene A could be associated with MeCP2 in some cells within a population and with MBD2 in other cells of the same type.