Abstract
Deoxyribonucleic acid methylation is a long known epigenetic mark involved in many biological processes and the ‘readers’ of this mark belong to several distinct protein families that ‘read’ and ‘translate’ the methylation mark into a function. Methyl-CpG binding domain proteins belong to one of these families that are associated with transcriptional activation/repression, regulation of chromatin structure, pluripotency, development, and differentiation. Discovered decades ago, the systematic determination of the genomic binding sites of these readers and their epigenome make-up at a genome-wide level revealed the tip of the functional iceberg. This review focuses on two members of the methyl binding proteins, namely MBD2 and MBD3 that reside in very similar complexes, yet appear to have very different biological roles. We provide a comprehensive comparison of their genome-wide binding features and emerging roles in gene regulation.
Highlights
DNA METHYLATION DNA methylation of cytosine residues was reported to be involved in gene silencing as early as 1975 (Holliday and Pugh, 1975; Holliday, 1989) and represents the first epigenetic mark (Holliday, 1989)
CONCLUDING REMARKS Since its discovery in 1975, DNA methylation has been one of the best studied epigenetic marks and the readers of DNA methylation that translate the signal of methylated DNA into a function or activity have obtained a lot of attention
The emerging picture is that MBD2 binds to CpG-rich, densely methylated DNA in vivo, with an apparent but not understood preference for promoter regions
Summary
DNA METHYLATION DNA methylation of cytosine residues was reported to be involved in gene silencing as early as 1975 (Holliday and Pugh, 1975; Holliday, 1989) and represents the first epigenetic mark (Holliday, 1989). Cases of highly dynamic regulation of DNA methylation were reported by the Gannon and Reid laboratories (Kangaspeska et al, 2008; Metivier et al, 2008), suggesting cyclical methylation/demethylation at promoters as a part of the transcription cycle at least at some promoters. They showed that the process involves DNA methyltransferases (DNMTs) as well as thymine-DNA-glycosylase (Tdg). Crystal structure of the MBD domain, in complex with www.frontiersin.org
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