Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 364, Issue 3, Pages 515-521Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.10.057
Keywords
thiazolidinedione (TZD); selective peroxisome proliferator-activated receptor modulator (SPPARM); microarray; chromatin immunoprecipitation; transcription; 3T3-L1 adipocytes
Categories
Funding
- NIDDK NIH HHS [KO1-DK62025, R01-DK33651, K01 DK062025-02, R01 DK033651, K01 DK062025-03, K01 DK062025, K01 DK062025-01, R01 DK033651-17] Funding Source: Medline
Ask authors/readers for more resources
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 EC50 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. (C) 2007 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available