DNA methylation is a stable epigenetic mark in plant and vertebrate genomes; it is implicated in regulation of higher order chromatin structure, maintenance of genome integrity, and stable patterns of gene expression. Biological effects of DNA methylation are, at least in part, mediated by proteins that preferentially bind to methylated DNA. It is now recognized that several structurally unrelated protein folds have the ability to recognize methylated CpGs in vitro and in vivo. In this chapter, we focus on the three major families of methyl-CpG-binding proteins: the MBD protein family, Kaiso and Kaiso-like proteins, and SRA domain proteins. We discuss the structural bases of methyl-CpG recognition, the function and specific properties of individual proteins, and their role in human disease such as Rett syndrome and cancer.
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