Methyl CpG-binding protein

Three of the MBD family members, namely MeCP2, MBDl, and MBD2, have been shown to act as transcriptional repressors in vitro and in cell culture assays in vivo [86-89,75,76]. Initially it was proposed that methyl-CpG binding proteins inhibit transcription directly, by binding to methylated DNA and blocking the access of transcription factors to their sites at gene promoters. It was soon... 

Fig. 8. Proposed models that link histone methylation to DNA methylation (for details see Section 5.2). Methylated cytosines attract histone methyltransferases that contain a methyl-binding domain or a methyl-CpG binding protein (MeCP2) that recruits histone methylase activities these introduce methyl groups into the histone tails. The binding of chromodomain HPl proteins to H3 tails methylated at lysine 9 generates a secondary layer of repressive chromatin structure, (b) In a reverse scenario, methylated histone tails attract chromodomain-binding proteins, which in turn recruit Dmnts to methylate adjacent DNA sequences.

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Nan X, Ng H.H., Johnson C.A., Laherty CD., Turner B.M., Eisenman R.N. and Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex (1998) Nature 393, 386-389... 

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Young Jl, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB et al (2005) Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci U S A 102 17551-17558... 

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The deacteylase complexes are targeted to specific promotors by interactions with different types of negative regulatory proteins. Among these are sequence-specific DNA-binding proteins, corepressors and the methylated CpG-binding proteins (see Section 1.4.8)... 

Methylation of DNA at CpG sequences. Methylated CpG elements are recognized by methyl-CpG binding proteins that recruit histone deacetylase activity and thereby induce an inhibitory chromatin configuration. 

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