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Science 298 (5599): 1747-1752

Copyright © 2002 by the American Association for the Advancement of Science

Corepressor-Dependent Silencing of Chromosomal Regions Encoding Neuronal Genes

Victoria V. Lunyak,1 Robert Burgess,1* Gratien G. Prefontaine,1 Charles Nelson,1 Sing-Hoi Sze,2 Josh Chenoweth,3 Phillip Schwartz,4 Pavel A. Pevzner,2 Christopher Glass,5 Gail Mandel,3 Michael G. Rosenfeld1dagger

The molecular mechanisms by which central nervous system-specific genes are expressed only in the nervous system and repressed in other tissues remain a central issue in developmental and regulatory biology. Here, we report that the zinc-finger gene-specific repressor element RE-1 silencing transcription factor/neuronal restricted silencing factor (REST/NRSF) can mediate extraneuronal restriction by imposing either active repression via histone deacetylase recruitment or long-term gene silencing using a distinct functional complex. Silencing of neuronal-specific genes requires the recruitment of an associated corepressor, CoREST, that serves as a functional molecular beacon for the recruitment of molecular machinery that imposes silencing across a chromosomal interval, including transcriptional units that do not themselves contain REST/NRSF response elements.

1 Howard Hughes Medical Institute (HHMI),
2 Department of Computer Science and Engineering, School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA.
3 Howard Hughes Medical Institute, Department of Neurobiology, State University of New York, Stony Brook, NY 11794, USA.
4 Affinity BioReagents, Incorporated, 14818 West 6th Avenue, Suite 10A, Golden, CO 80401, USA.
5 Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
*   Present address: Beckman Institute for Biomedical Research, Department of Functional Genomics, Temecula, CA 92590, USA.

dagger    To whom correspondence should be addressed. E-mail: mrosenfeld{at}ucsd.edu

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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882