First Author | Li SF | Year | 2013 |
Journal | Am J Physiol Endocrinol Metab | Volume | 304 |
Issue | 9 | Pages | E990-8 |
PubMed ID | 23512806 | Mgi Jnum | J:198118 |
Mgi Id | MGI:5495562 | Doi | 10.1152/ajpendo.00608.2012 |
Citation | Li SF, et al. (2013) G9a is transactivated by C/EBPbeta to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation. Am J Physiol Endocrinol Metab 304(9):E990-8 |
abstractText | In 3T3-L1 preadipocyte differentiation, the CCAAT/enhancer-binding protein-beta (C/EBPbeta) is an important early transcription factor that activates cell cycle genes during mitotic clonal expansion (MCE), sequentially activating peroxisome proliferator-activated receptor-gamma (PPARgamma) and C/EBPalpha during terminal differentiation. Although C/EBPbeta acquires its DNA binding activity via dual phosphorylation at about 12-16 h postinduction, the expression of PPARgamma and C/EBPalpha is not induced until 36-72 h. The delayed expression of PPARgamma and C/EBPalpha ensures the progression of MCE, but the mechanism responsible for the delay remains elusive. We provide evidence that G9a, a major euchromatic methyltransferase, is transactivated by C/EBPbeta and represses PPARgamma and C/EBPalpha through H3K9 dimethylation of their promoters during MCE. Inhibitor- or siRNA-mediated G9a downregulation modestly enhances PPARgamma and C/EBPalpha expression and adipogenesis in 3T3-L1 preadipocytes. Conversely, forced expression of G9a impairs the accumulation of triglycerides. Thus, this study elucidates an epigenetic mechanism for the delayed expression of PPARgamma and C/EBPalpha. |