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SWItching off methylated DNA

Nature Genetics volume 37, pages 212–213 (2005)Cite this article

The mechanism by which cytosine methylation stably represses transcription is of great interest. A new study provides evidence associating DNA methylation, MeCP2 and the SWI/SNF chromatin-remodeling factor, implicating local chromatin architecture in DNA methylation–dependent transcriptional repression.

In eukaryotes, the most abundant covalent modification of DNA is methylation of cytosine residues at carbon 5 of the pyrimidine ring. This modification occurs primarily in the context of a simple sequence (5′-CG-3′) and affects both strands of DNA. CpG methylation serves to increase the coding capacity of the genome—in essence, methylated carbon 5 serves as a 'fifth base' in DNA. Regions of the genome with high levels of methylated CpG dinucleotides include the inactive X chromosome in female mammals, imprinted genes and transposons and their relics1, all of which are associated with stable transcriptional repression. How does the cell read this information? Additionally, as CpG methylation is strongly associated with regions of the genome subject to stable transcriptional repression, how do cells convert the information embedded in cytosine methylation into a functional state? On page 254 of this issue, Harikrishnan N and colleagues2 identify an association between the methyl CpG binding protein MeCP2 and human Brahma (Brm), an ATPase subunit of the human SWI/SNF complex involved in chromatin remodeling. These findings establish a link between DNA methylation and chromatin structure and provide a new perspective on the mechanism of methylation-dependent gene regulation.

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Figure 1: One potential scenario by which MeCP2 and the SWI/SNF complex might cooperate in establishment or maintenance of transcriptional repression at a methylated locus.

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  1. the Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, 27709, North Carolina, USA

    Paul A Wade

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  1. Paul A Wade
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Wade, P. SWItching off methylated DNA. Nat Genet 37, 212–213 (2005). https://doi.org/10.1038/ng0305-212

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  • DOI: https://doi.org/10.1038/ng0305-212

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