| First Author | Zhang ZC | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 12 | Pages | 2330-8 |
| PubMed ID | 24732798 | Mgi Jnum | J:221625 |
| Mgi Id | MGI:5641147 | Doi | 10.1128/MCB.00070-14 |
| Citation | Zhang ZC, et al. (2014) Suv39h1 mediates AP-2alpha-dependent inhibition of C/EBPalpha expression during adipogenesis. Mol Cell Biol 34(12):2330-8 |
| abstractText | Previous studies have shown that CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays a very important role during adipocyte terminal differentiation and that AP-2alpha (activator protein 2alpha) acts as a repressor to delay the expression of C/EBPalpha. However, the mechanisms by which AP-2alpha prevents the expression of C/EBPalpha are not fully understood. Here, we present evidence that Suv39h1, a histone H3 lysine 9 (H3K9)-specific trimethyltransferase, and G9a, a euchromatic methyltransferase, both interact with AP-2alpha and enhance AP-2alpha-mediated transcriptional repression of C/EBPalpha. Interestingly, we discovered that G9a mediates dimethylation of H3K9, thus providing the substrate, which is methylated by Suv39h1, to H3K9me3 on the C/EBPalpha promoter. The expression level of AP-2alpha was consistent with enrichment of H3K9me2 and H3K9me3 on the C/EBPalpha promoter in 3T3-L1 preadipocytes. Knockdown of Suv39h markedly increased C/EBPalpha expression and promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed C/EBPalpha expression and impaired the accumulation of triglyceride, while simultaneous knockdown of AP-2alpha or G9a partially rescued this process. These findings indicate that Suv39h1 enhances AP-2alpha-mediated transcriptional repression of C/EBPalpha in an epigenetic manner and further inhibits adipocyte differentiation. |
