Transcriptional Repression by the SMRT-mSin3 Corepressor: Multiple Interactions, Multiple Mechanisms, and a Potential Role for TFIIB

ABSTRACT

A variety of eukaryotic transcription factors, including the nuclear hormone receptors, Max-Mad, BCL-6, and PLZF, appear to mediate transcriptional repression through the ability to recruit a multiprotein corepressor complex to the target promoter. This corepressor complex includes the SMRT/N-CoR polypeptides, mSin3A or -B, and histone deacetylase 1 or 2. The presence of a histone-modifying activity in the corepressor complex has led to the suggestion that gene silencing is mediated by modification of the chromatin template, perhaps rendering it less accessible to the transcriptional machinery. We report here, however, that the corepressor complex actually appears to exhibit multiple mechanisms of transcriptional repression, only one of which corresponds with detectable recruitment of the histone deacetylase. We provide evidence instead of an alternative pathway of repression that may be mediated by direct physical interactions between components of the corepressor complex and the general transcription factor TFIIB.

ACKNOWLEDGMENTS

We are indebted to D. Ayer, R. N. Eisenman, C. A. Hassig, M. A. Lazar, M. G. Rosenfeld, and S. L. Schreiber for generously providing molecular clones. We also thank Shelly Meeuson and Linfong Tzeng, who, as rotation students, assisted with some of the recombinant constructs, and Valentina Taryanik for technical help.

This work was supported by Public Health Service grant CA53394 from the National Cancer Institute.