| First Author | Song Z | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 21 | Pages | 8918-8932 |
| PubMed ID | 28351837 | Mgi Jnum | J:243673 |
| Mgi Id | MGI:5909372 | Doi | 10.1074/jbc.M117.776229 |
| Citation | Song Z, et al. (2017) Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer-binding protein alpha. J Biol Chem 292(21):8918-8932 |
| abstractText | Brown adipose tissue is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms of adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic KO of CycC completely blocked the differentiation process. RNA sequencing analyses of CycC-KD revealed a critical role of CycC in activating genes co-regulated by peroxisome proliferator activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha). Overexpression of PPARgamma2 or addition of the PPARgamma ligand rosiglitazone rescued the defects in CycC-KO brown preadipocytes and efficiently activated the PPARgamma-responsive promoters in both WT and CycC-KO cells, suggesting that CycC is not essential for PPARgamma transcriptional activity. In contrast, CycC-KO significantly reduced C/EBPalpha-dependent gene expression. Unlike for PPARgamma, overexpression of C/EBPalpha could not induce C/EBPalpha target gene expression in CycC-KO cells or rescue the CycC-KO defects in brown adipogenesis, suggesting that CycC is essential for C/EBPalpha-mediated gene activation. CycC physically interacted with C/EBPalpha, and this interaction was required for C/EBPalpha transactivation domain activity. Consistent with the role of C/EBPalpha in white adipogenesis, CycC-KD also inhibited differentiation of 3T3-L1 cells into white adipocytes. Together, these data indicate that CycC activates adipogenesis in part by stimulating the transcriptional activity of C/EBPalpha. |
