Selective modulation of promoter recruitment and transcriptional activity of PPARγ

Dorothy D. Sears, Albert Hsiao, Jachelle M. Ofrecio, Justin Chapman, Weimin He, Jerrold M. Olefsky

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor regulated by the insulin-sensitizing thiazolidinediones (TZDs). We studied selective modulation of endogenous genes by PPARγ 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 PPARγ recruitment to target gene promoters. Selective modulation of PPARγ by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes.

Original languageEnglish (US)
Pages (from-to)515-521
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume364
Issue number3
DOIs
StatePublished - Dec 21 2007

Keywords

  • 3T3-L1 adipocytes
  • Chromatin immunoprecipitation
  • Microarray
  • Selective peroxisome proliferator-activated receptor modulator (SPPARM)
  • Thiazolidinedione (TZD)
  • Transcription

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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