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Molecular and Cellular Biology, October 1998, p. 5724-5733, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Transcriptional Silencing Is Defined by Isoform- and Heterodimer-Specific Interactions between Nuclear Hormone Receptors and Corepressors

Chi-Wai Wong and Martin L. Privalsky*

Section of Microbiology, Division of Biological Sciences, University of California at Davis, Davis, California 95616

Received 4 February 1998/Returned for modification 27 April 1998/Accepted 7 July 1998

Nuclear hormone receptors are ligand-regulated transcription factors that play critical roles in metazoan homeostasis, development, and reproduction. Many nuclear hormone receptors exhibit bimodal transcriptional properties and can either repress or activate the expression of a given target gene. Repression appears to require a physical interaction between a receptor and a corepressor complex containing the SMRT/TRAC or N-CoR/RIP13 polypeptides. We wished to better elucidate the rules governing the association of receptors with corepressors. We report here that different receptors interact with different domains in the SMRT and N-CoR corepressors and that these divergent interactions may therefore contribute to distinct repression phenotypes. Intriguingly, different isoforms of a single nuclear hormone receptor class also differ markedly in their interactions with corepressors, indicative of their nonidentical actions in cellular regulation. Finally, we present evidence that combinatorial interactions between different receptors can, through the formation of heterodimeric receptors, result in novel receptor-corepressor interactions not observed for homomeric receptors.

* Corresponding author. Mailing address: Section of Microbiology, Division of Biological Sciences, One Shields Ave., University of California at Davis, Davis, CA 95616. Phone: (530) 752-3013. Fax: (530) 752-9014. E-mail: mlprivalsky{at}ucdavis.edu.

Molecular and Cellular Biology, October 1998, p. 5724-5733, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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