The G0/G1 switch gene 2 is a novel PPAR target gene

Fokko Zandbergen, Stéphane Mandard, Pascal Escher, Nguan Soon Tan, David Patsouris, Tim Jatkoe, Sandra Rojas-Caro, Steve Madore, Walter Wahli, Sherrie Tafuri, Michael Müller, Sander Kersten

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

PPARs (peroxisome-proliferator-activated receptors) alpha, beta/delta and gamma are a group of transcription factors that are involved in numerous processes, including lipid metabolism and adipogenesis. By comparing liver mRNAs of wild-type and PPARalpha-null mice using microarrays, a novel putative target gene of PPARalpha, G0S2 (G0/G1 switch gene 2), was identified. Hepatic expression of G0S2 was up-regulated by fasting and by the PPARalpha agonist Wy14643 in a PPARalpha-dependent manner. Surprisingly, the G0S2 mRNA level was highest in brown and white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human SGBS (Simpson-Golabi-Behmel syndrome) adipogenesis. Transactivation, gel shift and chromatin immunoprecipitation assays indicated that G0S2 is a direct PPARgamma and probable PPARalpha target gene with a functional PPRE (PPAR-responsive element) in its promoter. Up-regulation of G0S2 mRNA seemed to be specific for adipogenesis, and was not observed during osteogenesis or myogenesis. In 3T3-L1 fibroblasts, expression of G0S2 was associated with growth arrest, which is required for 3T3-L1 adipogenesis. Together, these data indicate that G0S2 is a novel target gene of PPARs that may be involved in adipocyte differentiation.
Original languageEnglish
Pages (from-to)313-24
Number of pages12
JournalBiochemical Journal
Volume392
Issue numberPt 2
DOIs
Publication statusPublished - 1 Dec 2005

Keywords

  • Adipocytes
  • Adipogenesis
  • Animals
  • Base Sequence
  • Cell Cycle Proteins
  • Cell Line
  • Endoplasmic Reticulum
  • Gene Deletion
  • Hepatocytes
  • Humans
  • Liver
  • Male
  • Mice
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • PPAR alpha
  • Promoter Regions, Genetic
  • Protein Transport
  • RNA, Messenger
  • Rats
  • Response Elements
  • Sequence Homology, Nucleic Acid
  • Substrate Specificity
  • Up-Regulation

Cite this