Methyl-CpG binding proteins: specialized transcriptional repressors or structural components of chromatin?

DNA methylation is an epigenetic modification that is implicated in transcriptional silencing. It is becoming increasingly clear that both correct levels and proper interpretation of DNA methylation are important for normal development and function of many organisms, including humans. In this review we focus on recent advances in understanding how proteins that bind to methylated DNA recognize their binding sites and translate the DNA methylation signal into functional states of chromatin. Although the function of methyl-CpG binding proteins in transcriptional repression has been attributed to their cooperation with co-repressor complexes, additional roles for these proteins in chromatin compaction and spatial organization of nuclear domains have also been proposed. Finally, we provide a brief overview of how methyl-CpG proteins contribute to human disease processes such as Rett syndrome and cancer.