Suv39h1 mediates AP-2?-dependent inhibition of C/EBP? expression during adipogenesis.

ABSTRACT: Previous studies have shown that CCAAT/enhancer-binding protein ? (C/EBP?) plays a very important role during adipocyte terminal differentiation and that AP-2? (activator protein 2?) acts as a repressor to delay the expression of C/EBP?. However, the mechanisms by which AP-2? prevents the expression of C/EBP? 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-2? and enhance AP-2?-mediated transcriptional repression of C/EBP?. Interestingly, we discovered that G9a mediates dimethylation of H3K9, thus providing the substrate, which is methylated by Suv39h1, to H3K9me3 on the C/EBP? promoter. The expression level of AP-2? was consistent with enrichment of H3K9me2 and H3K9me3 on the C/EBP? promoter in 3T3-L1 preadipocytes. Knockdown of Suv39h markedly increased C/EBP? expression and promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed C/EBP? expression and impaired the accumulation of triglyceride, while simultaneous knockdown of AP-2? or G9a partially rescued this process. These findings indicate that Suv39h1 enhances AP-2?-mediated transcriptional repression of C/EBP? in an epigenetic manner and further inhibits adipocyte differentiation.

SUBMITTER: Zhang ZC 

PROVIDER: S-EPMC4054298 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature