Combinatorial Roles of the Nuclear Receptor Corepressor in Transcription and Development

Thandi M. Onami, University of Tennessee - Knoxville
Kristen Jepsen, University of California - San Diego
Ola Hermanson, University of California - San Diego
Anatoli S. Anatoli S. Gleiberman, University of California - San Diego
Victoria Lunyak, University of California - San Diego
Robert J. McEvilly, University of California - San Diego
Riki Kurokawa, University of California - San Diego
Vivek Kumar, University of California - San Diego
Forrest Liu, University of California - San Diego
Edward Seto, University of South Florida
Stephen M. Hedrick, University of California - San Diego
Gail Mandel, STATE UNIVERSITY OF NEW YORK S
Christopher K. Glass, University of California - San Diego
David W. Rose, University of California - San Diego
Michael G. Rosenfeld, University of California - San Diego

Abstract

Transcriptional repression plays crucial roles in diverse aspects of metazoan development, implying critical regulatory roles for corepressors such as N-CoR and SMRT. Altered patterns of transcription in tissues and cells derived from N-CoR gene–deleted mice and the resulting block at specific points in CNS, erythrocyte, and thymocyte development indicated that N-CoR was a required component of short-term active repression by nuclear receptors and MAD and of a subset of long-term repression events mediated by REST/NRSF. Unexpectedly, N-CoR and a specific deacetylase were also required for transcriptional activation of one class of retinoic acid response element. Together, these findings suggest that specific combinations of corepressors and histone deacetylases mediate the gene-specific actions of DNA-bound repressors in development of multiple organ systems.