TY - JOUR
T1 - The nuclear receptor corepressors NCoR and SMRT decrease peroxisome proliferator-activated receptor γ transcriptional activity and repress 3T3-L1 adipogenesis
AU - Yu, Christine
AU - Markan, Kathleen
AU - Temple, Karla A.
AU - Deplewski, Dianne
AU - Brady, Matthew J.
AU - Cohen, Ronald N.
PY - 2005/4/8
Y1 - 2005/4/8
N2 - The peroxisome proliferator-activated receptor γ (PPARγ) is a central regulator of adipogenesis and recruits coactivator proteins in response to ligand. However, the role of another class of nuclear cofactors, the nuclear receptor corepressors, in modulating PPARγ transcriptional activity is less clear. Such corepressors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT). Our data suggest that PPARγ recruits SMRT and NCoR in the absence of ligand and that these corepressors are capable of down-regulating PPARγ-mediated transcriptional activity. The addition of the PPARγ ligand pioglitazone results in dissociation of the PPARγ-corepressor complex. To define the role of SMRT and NCoR in PPARγ action, 3T3-L1 cells deficient in SMRT or NCoR were generated by RNA interference. When these cells are exposed to differentiation media, they exhibit increased expression of adipocyte-specific genes and increased production of lipid droplets, as compared with control cells. These data suggest that the nuclear receptor corepressors decrease PPARγ transcriptional activity and repress the adipogenic program in 3T3-L1 cells.
AB - The peroxisome proliferator-activated receptor γ (PPARγ) is a central regulator of adipogenesis and recruits coactivator proteins in response to ligand. However, the role of another class of nuclear cofactors, the nuclear receptor corepressors, in modulating PPARγ transcriptional activity is less clear. Such corepressors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT). Our data suggest that PPARγ recruits SMRT and NCoR in the absence of ligand and that these corepressors are capable of down-regulating PPARγ-mediated transcriptional activity. The addition of the PPARγ ligand pioglitazone results in dissociation of the PPARγ-corepressor complex. To define the role of SMRT and NCoR in PPARγ action, 3T3-L1 cells deficient in SMRT or NCoR were generated by RNA interference. When these cells are exposed to differentiation media, they exhibit increased expression of adipocyte-specific genes and increased production of lipid droplets, as compared with control cells. These data suggest that the nuclear receptor corepressors decrease PPARγ transcriptional activity and repress the adipogenic program in 3T3-L1 cells.
UR - http://www.scopus.com/inward/record.url?scp=17144395146&partnerID=8YFLogxK
U2 - 10.1074/jbc.M409468200
DO - 10.1074/jbc.M409468200
M3 - Article
C2 - 15691842
AN - SCOPUS:17144395146
SN - 0021-9258
VL - 280
SP - 13600
EP - 13605
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -