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

L Nagy, HY Kao, D Chakravarti, RJ Lin, CA Hassig… - Cell, 1997 - cell.com
L Nagy, HY Kao, D Chakravarti, RJ Lin, CA Hassig, DE Ayer, SL Schreiber, RM Evans
Cell, 1997cell.com
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 …
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.
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