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

56 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Personnel Selection
Thiazolidinediones
PPAR gamma
Modulation
rosiglitazone
Genes
pioglitazone
troglitazone
Kinetics
Chromatin
Ligands
Acetylation
Chromatin Assembly and Disassembly
Chromatin Immunoprecipitation
Transcription
Microarrays
Cytoplasmic and Nuclear Receptors
Adipocytes
Histones
Chemical activation

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

Cite this

Selective modulation of promoter recruitment and transcriptional activity of PPARγ. / Sears, Dorothy D.; Hsiao, Albert; Ofrecio, Jachelle M.; Chapman, Justin; He, Weimin; Olefsky, Jerrold M.

In: Biochemical and Biophysical Research Communications, Vol. 364, No. 3, 21.12.2007, p. 515-521.

Research output: Contribution to journalArticle

Sears, Dorothy D. ; Hsiao, Albert ; Ofrecio, Jachelle M. ; Chapman, Justin ; He, Weimin ; Olefsky, Jerrold M. / Selective modulation of promoter recruitment and transcriptional activity of PPARγ. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 364, No. 3. pp. 515-521.
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