HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 38, 28237-28245, September 21, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/38/28237    most recent M704304200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nikitina, T. Articles by Woodcock, C. L. Search for Related Content PubMed PubMed Citation Articles by Nikitina, T. Articles by Woodcock, C. L. Social Bookmarking                      What's this?

MeCP2-Chromatin Interactions Include the Formation of Chromatosome-like Structures and Are Altered in Mutations Causing Rett Syndrome^*

Tatiana Nikitina, Rajarshi P. Ghosh, Rachel A. Horowitz-Scherer, Jeffrey C. Hansen^¶, Sergei A. Grigoryev^||, and Christopher L. Woodcock¹

From the Department of Biology, University of Massachusetts, Amherst, Massachusetts 01003, the Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, Massachusetts 01003, the ^¶Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, and the ^||Department of Biochemistry and Molecular Biology H-171, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

hMeCP2 (human methylated DNA-binding protein 2), mutations of which cause most cases of Rett syndrome (RTT), is involved in the transmission of repressive epigenetic signals encoded by DNA methylation. The present work focuses on the modifications of chromatin architecture induced by MeCP2 and the effects of RTT-causing mutants. hMeCP2 binds to nucleosomes close to the linker DNA entry-exit site and protects 11 bp of linker DNA from micrococcal nuclease. MeCP2 mutants differ in this property; the R106W mutant gives very little extra protection beyond the 146-bp nucleosome core, whereas the large C-terminal truncation R294X reveals wild type behavior. Gel mobility assays show that linker DNA is essential for proper MeCP2 binding to nucleosomes, and electron microscopy visualization shows that the protein induces distinct conformational changes in the linker DNA. When bound to nucleosomes, MeCP2 is in close proximity to histone H3, which exits the nucleosome core close to the proposed MeCP2-binding site. These findings firmly establish nucleosomal linker DNA as a crucial binding partner of MeCP2 and show that different RTT-causing mutations of MeCP2 are correspondingly defective in different aspects of the interactions that alter chromatin architecture.

Received for publication, May 24, 2007 , and in revised form, July 13, 2007.

^* This work was supported in part by National Institutes of Health Grant GM070897 and funds from the International Rett Syndrome Foundation (to C. L. W.), National Institutes of Health Grants GM45916 and GM66834 (to J. C. H.), and National Science Foundation Grant MCB-0615536 (to S. A. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Biology Dept., University of Massachusetts, Amherst, MA 01003. Tel.: 413-545-2825; Fax: 413-545-3243; E-mail: chris{at}bio.umass.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Wang, M. Li, S. Stadler, S. Correll, P. Li, D. Wang, R. Hayama, L. Leonelli, H. Han, S. A. Grigoryev, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation J. Cell Biol., January 26, 2009; 184(2): 205 - 213. [Abstract] [Full Text] [PDF]

				J. Singh, A. Saxena, J. Christodoulou, and D. Ravine MECP2 genomic structure and function: insights from ENCODE Nucleic Acids Res., November 1, 2008; 36(19): 6035 - 6047. [Abstract] [Full Text] [PDF]

				R. P. Ghosh, R. A. Horowitz-Scherer, T. Nikitina, L. M. Gierasch, and C. L. Woodcock Rett Syndrome-causing Mutations in Human MeCP2 Result in Diverse Structural Changes That Impact Folding and DNA Interactions J. Biol. Chem., July 18, 2008; 283(29): 20523 - 20534. [Abstract] [Full Text] [PDF]