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

Research output: Contribution to journalArticle

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
Externally publishedYes

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Co-Repressor Proteins
Histone Deacetylases
Cytoplasmic and Nuclear Receptors
Histone Deacetylase 1
Basic Helix-Loop-Helix Transcription Factors
Thyroid Hormone Receptors
Histone Deacetylase Inhibitors
Myeloid Leukemia
HL-60 Cells
Retinoids
Tretinoin
Yeast
Genes
Yeasts
Hormones
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nagy, L., Kao, H. Y., Chakravarti, D., Lin, R. J., Hassig, C. A., Ayer, D. E., ... Evans, R. M. (1997). Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell, 89(3), 373-380. https://doi.org/10.1016/S0092-8674(00)80218-4

Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. / Nagy, Laszlo; Kao, Hung Ying; Chakravarti, Debabrata; Lin, Richard J.; Hassig, Christian A.; Ayer, Donald E.; Schreiber, Stuart L.; Evans, Ronald M.

In: Cell, Vol. 89, No. 3, 02.05.1997, p. 373-380.

Research output: Contribution to journalArticle

Nagy, L, Kao, HY, Chakravarti, D, Lin, RJ, Hassig, CA, Ayer, DE, Schreiber, SL & Evans, RM 1997, 'Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase', Cell, vol. 89, no. 3, pp. 373-380. https://doi.org/10.1016/S0092-8674(00)80218-4
Nagy, Laszlo ; Kao, Hung Ying ; Chakravarti, Debabrata ; Lin, Richard J. ; Hassig, Christian A. ; Ayer, Donald E. ; Schreiber, Stuart L. ; Evans, Ronald M. / Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. In: Cell. 1997 ; Vol. 89, No. 3. pp. 373-380.
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