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Mol Cell. 2008 Feb 29;29(4):525-31. doi: 10.1016/j.molcel.2007.12.028.

MeCP2 binding to DNA depends upon hydration at methyl-CpG.

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  • 1School of Biological Sciences, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.

Abstract

MeCP2 is an essential transcriptional repressor that mediates gene silencing through binding to methylated DNA. Binding specificity has been thought to depend on hydrophobic interactions between cytosine methyl groups and a hydrophobic patch within the methyl-CpG-binding domain (MBD). X-ray analysis of a methylated DNA-MBD cocrystal reveals, however, that the methyl groups make contact with a predominantly hydrophilic surface that includes tightly bound water molecules. This suggests that MeCP2 recognizes hydration of the major groove of methylated DNA rather than cytosine methylation per se. The MeCP2-DNA complex also identifies a unique structural role for T158, the residue most commonly mutated in Rett syndrome.

PMID:
18313390
DOI:
10.1016/j.molcel.2007.12.028
[PubMed - indexed for MEDLINE]
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