| First Author | Jin Q | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 19 | Pages | 3746-53 |
| PubMed ID | 25071153 | Mgi Jnum | J:224343 |
| Mgi Id | MGI:5662043 | Doi | 10.1128/MCB.00622-14 |
| Citation | Jin Q, et al. (2014) Gcn5 and PCAF regulate PPARgamma and Prdm16 expression to facilitate brown adipogenesis. Mol Cell Biol 34(19):3746-53 |
| abstractText | 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 PPARgamma, thereby preventing adipocyte differentiation. The adipogenesis defects in Gcn5/PCAF DKO cells are rescued by ectopic expression of peroxisome proliferator-activated receptor gamma (PPARgamma), suggesting Gcn5/PCAF act upstream of PPARgamma to facilitate adipogenesis. The requirement of Gcn5/PCAF for PPARgamma expression was unexpectedly bypassed by prolonged treatment with an adipogenic inducer, 3-isobutyl-1-methylxanthine (IBMX). However, neither PPARgamma 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 PPARgamma and Prdm16 expression at different steps in the transcription process, facilitating RNA polymerase II recruitment to Prdm16 and elongation of PPARgamma transcripts. Overall, our study reveals that Gcn5/PCAF facilitate adipogenesis through regulation of PPARgamma expression and regulate brown adipogenesis by influencing Prdm16 expression. |
