Zhang ZC, Liu Y, Li SF, Guo L, Zhao Y, Qian SW, Wen B, Tang QQ, Li X
Previous studies show that CCAAT/enhancer-binding protein α (C/EBPα) plays a very important role during adipocyte terminal differentiation and that AP-2α (Activator Protein 2α) acts as a repressor to delay the expression of C/EBPα. However, the mechanisms by which AP-2α prevents the expression of C/EBPα 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-2α and enhance AP-2α-mediated transcriptional repression of C/EBPα. Interestingly, we discovered that G9a mediated dimethylation of H3K9, thus providing the substrate which is methylated by Suv39h1 to H3K9me3 on the C/EBPα promoter. The expression level of AP-2α was consistent with enrichment of H3K9me2 and H3K9me3 on the C/EBPα promoter in 3T3-L1 preadipocytes. Knockdown of Suv39h markedly increased C/EBPα expression and promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed C/EBPα expression and impaired the accumulation of triglyceride, while simultaneous knockdown of AP-2α or G9a partially rescued this process. These findings indicate that Suv39h1 enhances AP-2α-mediated transcriptional repression of C/EBPα in an epigenetic manner and further inhibits adipocyte differentiation.