Combinatorial roles of the nuclear receptor corepressor in transcription and development

Kristen Jepsen, Ola Hermanson, Thandi M. Onami, Anatoli S. Gleiberman, Victoria Lunyak, Robert J. McEvilly, Riki Kurokawa, Vivek Kumar, Forrest Liu, Edward Seto, Stephen M. Hedrick, Gail Mandel, Christopher K. Glass, David W. Rose, Michael G. Rosenfeld

Research output: Contribution to journalArticlepeer-review

438 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)753-763
Number of pages11
JournalCell
Volume102
Issue number6
DOIs
StatePublished - Sep 15 2000

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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