Cys₂His₂ Zinc Finger Methyl-CpG Binding Proteins: Getting a Handle on Methylated DNA

DNA methylation is an essential epigenetic modification involved in the maintenance of genomic stability, preservation of cellular identity, and regulation of the transcriptional landscape needed to maintain cellular function. In an increasing number of disease conditions, DNA methylation patterns are inappropriately distributed in a manner that supports the disease phenotype. Methyl-CpG binding proteins (MBPs) are specialized transcription factors that read and translate methylated DNA signals into recruitment of protein assemblies that can alter local chromatin architecture and transcription. MBPs thus play a key intermediary role in gene regulation for both normal and diseased cells. Here, we highlight established and potential structure-function relationships for the best characterized members of the zinc finger (ZF) family of MBPs in propagating DNA methylation signals into downstream cellular responses. Current and future investigations aimed toward expanding our understanding of ZF MBP cellular roles will provide needed mechanistic insight into normal and disease state functions, as well as afford evaluation for the potential of these proteins as epigenetic-based therapeutic targets.