Selective modulation of promoter recruitment and transcriptional activity of PPAR{gamma}
- Department of Medicine, University of California, San Diego, 9500 Gilman Drive, MC0673, La Jolla, CA 92093 (United States)
- Pfizer Inc., 10628 Science Center Drive, La Jolla, CA 92121 (United States)
Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) is a nuclear receptor regulated by the insulin-sensitizing thiazolidinediones (TZDs). We studied selective modulation of endogenous genes by PPAR{gamma} ligands using microarray, RNA expression kinetics, and chromatin immunoprecipitation (ChIP) in 3T3-L1 adipocytes. We found over 300 genes that were significantly regulated the TZDs pioglitazone, rosiglitazone, and troglitazone. TZD-mediated expression profiles were unique but overlapping. Ninety-one genes were commonly regulated by all three ligands. TZD time course and dose-response studies revealed gene- and TZD-specific expression kinetics. PEPCK expression was induced rapidly but PDK4 expression was induced gradually. Troglitazone EC{sub 50} values for PEPCK, PDK4, and RGS2 regulation were greater than those for pioglitazone and rosiglitazone. TZDs differentially induced histone acetylation of and PPAR{gamma} recruitment to target gene promoters. Selective modulation of PPAR{gamma} by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes.
- OSTI ID:
- 21033015
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 364, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.10.057; PII: S0006-291X(07)02183-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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