Gcn5 and PCAF regulate PPAR? and Prdm16 expression to facilitate brown adipogenesis.

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 PPAR?, thereby preventing adipocyte differentiation. The adipogenesis defects in Gcn5/PCAF DKO cells are rescued by ectopic expression of peroxisome proliferator-activated receptor ? (PPAR?), suggesting Gcn5/PCAF act upstream of PPAR? to facilitate adipogenesis. The requirement of Gcn5/PCAF for PPAR? expression was unexpectedly bypassed by prolonged treatment with an adipogenic inducer, 3-isobutyl-1-methylxanthine (IBMX). However, neither PPAR? 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 PPAR? and Prdm16 expression at different steps in the transcription process, facilitating RNA polymerase II recruitment to Prdm16 and elongation of PPAR? transcripts. Overall, our study reveals that Gcn5/PCAF facilitate adipogenesis through regulation of PPAR? expression and regulate brown adipogenesis by influencing Prdm16 expression.

SUBMITTER: Jin Q 

PROVIDER: S-EPMC4187735 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature