Combinatorial roles of the nuclear receptor corepressor in transcription and development

Transcriptional repression plays crucial roles in diverse aspects of metazo an development, implying critical regulatory roles for corepressors such as N-CoR and SMRT. Altered patterns of transcription in tissues and cells der ived from N-CoR gene-deleted mice and the resulting block at specific point s in CNS, erythrocyte, and thymocyte development indicated that N-CoR was a required component of short-term active repression by nuclear receptors an d 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 tran scriptional activation of one class of retinoic acid response element. Toge ther, these findings suggest that specific combinations of corepressors and histone deacetylases mediate the gene-specific actions of DNA-bound repres sors in development of multiple organ systems.