TY - JOUR
T1 - Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase
AU - Nagy, Laszlo
AU - Kao, Hung Ying
AU - Chakravarti, Debabrata
AU - Lin, Richard J.
AU - Hassig, Christian A.
AU - Ayer, Donald E.
AU - Schreiber, Stuart L.
AU - Evans, Ronald M.
N1 - Funding Information:
We thank Dr. John Schwabe for insight into domain structure of SMRT and vector design, Dr. Peter Tontonoz for help in the design and execution of the cell differentiation assays, and Drs. John Schwabe and Chuan Li for providing purified RAR–RXR heterodimers. We acknowledge Shun-Hua Chou for help in vector construction and analysis, Jackie Alvarez for technical assistance, Henry Juguilon for help in tissue culture, and Lita Ong and Elaine Stevens for administrative assistance. We thank Dr. Ron DePinho for communicating results prior to publication. We thank members of the Evans lab for providing reagents and critical reading of the manuscript. R. M. E. is an Investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies. D. C. is a Fellow of the Jane Coffin Childs Memorial Fund for Medical Research. R. J. L. is a predoctoral Fellow of the Lucille P. Markey Charitable Trust. This work was supported by the Howard Hughes Medical Institute and NIH grants GM26444 and HD27183. L. N. is on leave from the Department of Biochemistry, University Medical School, Debrecen, Hungary.
PY - 1997/5/2
Y1 - 1997/5/2
N2 - 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.
AB - 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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U2 - 10.1016/S0092-8674(00)80218-4
DO - 10.1016/S0092-8674(00)80218-4
M3 - Article
C2 - 9150137
AN - SCOPUS:0030953186
SN - 0092-8674
VL - 89
SP - 373
EP - 380
JO - Cell
JF - Cell
IS - 3
ER -