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Nucleic Acids Research 2005 33(20):6603-6609; doi:10.1093/nar/gki971
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Published online 27 November 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

Structure-specific binding of MeCP2 to four-way junction DNA through its methyl CpG-binding domain

Teca Calcagno Galvão and Jean O. Thomas*

Department of Biochemistry, University of Cambridge 80 Tennis Court Road, Cambridge CB2 1GA, UK

*To whom correspondence should be addressed. Tel: +44 1223 333670; Fax +44 1223 766002; Email: jot1{at}bioc.cam.ac.uk

Received August 9, 2005. Revised November 3, 2005. Accepted November 3, 2005.

MeCP2, whose methylated DNA-binding domain (MBD) binds preferentially to DNA containing 5Me-CpG relative to linear unmethylated DNA, also binds preferentially, and with similar affinity, to unmethylated four-way DNA junctions through the MBD. The Arg133Cys (R133C) mutation in the MBD, a Rett syndrome mutation that abolishes binding to methylated DNA, leads to only a slight reduction in the affinity of the MBD for four-way junctions, suggesting distinct but partially overlapping modes of binding to junction and methylated DNA. Binding to unmethylated DNA junctions is likely to involve a subset of the interactions that occur with methylated DNA. High-affinity, methylation-independent binding to four-way junctions is consistent with additional roles for MeCP2 in chromatin, beyond recognition of 5Me-CpG.

Present address: Teca Calcagno Galvão, Centro Nacional de Biotecnología, CSIC, Madrid 28049, Spain


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