Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase

Laszlo Nagy*, Hung Ying Kao, Debabrata Chakravarti, Richard J. Lin, Christian A. Hassig, Donald E. Ayer, Stuart L. Schreiber, Ronald M. Evans

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1069 Scopus citations

Abstract

The transcriptional corepressors SMRT and N-CoR function as silencing mediators for retinoid and thyroid hormone receptors. Here we show that SMRT and N-CoR directly interact with mSin3A, a corepressor for the Mad-Max heterodimer and a homolog of the yeast global-transcriptional repressor Sin3p. In addition, we demonstrate that the recently characterized histone deacetylase 1 (HDAC1) interacts with Sin3A and SMRT to form a multisubunit repressor complex. Consistent with this model, we find that HDAC inhibitors synergize with retinoic acid to stimulate hormone-responsive genes and differentiation of myeloid leukemia (HL-60) cells. This work establishes a convergence of repression pathways for bHLH-Zip proteins and nuclear receptors and suggests this type of regulation may be more widely conserved than previously suspected.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalCell
Volume89
Issue number3
DOIs
StatePublished - May 2 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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