Histone Methylation Regulator PTIP Is Required for PPARγ and C/EBPα Expression and Adipogenesis

Young Wook Cho, Sun Hwa Hong, Qihuang Jin, Lifeng Wang, Ji Eun Lee, Oksana Gavrilova, Kai Ge

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

PPARγ and C/EBPα cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARγ and C/EBPα expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARγ and C/EBPα expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARγ expression and PPARγ-stimulated C/EBPα expression. Further, PTIP is essential for induction of PPARγ and C/EBPα expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARγ and C/EBPα promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Rescue of the adipogenesis defect in PTIP-/- MEFs requires coexpression of PPARγ and C/EBPα. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight. Thus, by regulating PPARγ and C/EBPα expression, PTIP plays a critical role in adipogenesis.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalCell Metabolism
Volume10
Issue number1
DOIs
StatePublished - Jul 8 2009

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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