Gcn5 and PCAF regulate PPARγ and Prdm16 expression to facilitate brown adipogenesis

Qihuang Jin, Chaochen Wang, Xianghong Kuang, Xuesong Feng, Vittorio Sartorelli, Hao Ying, Kai Ge, Sharon Y.R. Dent

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The acetyltransferase Gcn5 is critical for embryogenesis and shows partial functional redundancy with its homolog PCAF. However, the tissue- and cell lineage-specific functions of Gcn5 and PCAF are still not well defined. Here we probe the functions of Gcn5 and PCAF in adipogenesis. We found that the double knockout (DKO) of Gcn5/PCAF inhibits expression of the master adipogenic transcription factor gene PPARγ, thereby preventing adipocyte differentiation. The adipogenesis defects in Gcn5/ PCAF DKO cells are rescued by ectopic expression of peroxisome proliferator-activated receptor γ (PPARγ), suggesting Gcn5/PCAF act upstream of PPARγ to facilitate adipogenesis. The requirement of Gcn5/PCAF for PPARγ expression was unexpectedly bypassed by prolonged treatment with an adipogenic inducer, 3-isobutyl-1-methylxanthine (IBMX). However, neither PPARγ ectopic expression nor prolonged IBMX treatment rescued defects in Prdm16 expression in DKO cells, indicating that Gcn5/PCAF are essential for normal Prdm16 expression. Gcn5/PCAF regulate PPARγ and Prdm16 expression at different steps in the transcription process, facilitating RNA polymerase II recruitment to Prdm16 and elongation of PPARγ transcripts. Overall, our study reveals that Gcn5/PCAF facilitate adipogenesis through regulation of PPARγ expression and regulate brown adipogenesis by influencing Prdm16 expression.

Original languageEnglish (US)
Pages (from-to)3746-3753
Number of pages8
JournalMolecular and cellular biology
Volume34
Issue number19
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Jin, Q., Wang, C., Kuang, X., Feng, X., Sartorelli, V., Ying, H., Ge, K., & Dent, S. Y. R. (2014). Gcn5 and PCAF regulate PPARγ and Prdm16 expression to facilitate brown adipogenesis. Molecular and cellular biology, 34(19), 3746-3753. https://doi.org/10.1128/MCB.00622-14