| First Author | Wang L | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 1 | Pages | 45-59 |
| PubMed ID | 23178591 | Mgi Jnum | J:192309 |
| Mgi Id | MGI:5464915 | Doi | 10.1038/emboj.2012.306 |
| Citation | Wang L, et al. (2013) Histone H3K9 methyltransferase G9a represses PPARgamma expression and adipogenesis. EMBO J 32(1):45-59 |
| abstractText | PPARgamma promotes adipogenesis while Wnt proteins inhibit adipogenesis. However, the mechanisms that control expression of these positive and negative master regulators of adipogenesis remain incompletely understood. By genome-wide histone methylation profiling in preadipocytes, we find that among gene loci encoding adipogenesis regulators, histone methyltransferase (HMT) G9a-mediated repressive epigenetic mark H3K9me2 is selectively enriched on the entire PPARgamma locus. H3K9me2 and G9a levels decrease during adipogenesis, which correlates inversely with induction of PPARgamma. Removal of H3K9me2 by G9a deletion enhances chromatin opening and binding of the early adipogenic transcription factor C/EBPbeta to PPARgamma promoter, which promotes PPARgamma expression. Interestingly, G9a represses PPARgamma expression in an HMT activity-dependent manner but facilitates Wnt10a expression independent of its enzymatic activity. Consistently, deletion of G9a or inhibiting G9a HMT activity promotes adipogenesis. Finally, deletion of G9a in mouse adipose tissues increases adipogenic gene expression and tissue weight. Thus, by inhibiting PPARgamma expression and facilitating Wnt10a expression, G9a represses adipogenesis. |
