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Science 327 (5968): 996-1000

Copyright © 2010 by the American Association for the Advancement of Science

Regulation of Alternative Splicing by Histone Modifications

Reini F. Luco,1 Qun Pan,2 Kaoru Tominaga,3 Benjamin J. Blencowe,2 Olivia M. Pereira-Smith,3 Tom Misteli1,*

Abstract: Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. We demonstrated a direct role for histone modifications in alternative splicing. We found distinctive histone modification signatures that correlate with the splicing outcome in a set of human genes, and modulation of histone modifications causes splice site switching. Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery.

1 National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2 Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
3 The Barshop Institute for Longevity and Aging Studies, Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78245-3207, USA.

* To whom correspondence should be addressed. E-mail: mistelit{at}

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