Suv39h1 mediates AP-2α-dependent inhibition of C/EBPα expression during adipogenesis

Zhi Chun Zhang, Yuan Liu, Shu Fen Li, Liang Guo, Yue Zhao, Shu Wen Qian, Bo Wen, Qi Qun Tang, Xi Li

Research output: Contribution to journalArticle

Abstract

Previous studies have shown 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 mediates 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.

Original languageEnglish (US)
Pages (from-to)2330-2338
Number of pages9
JournalMolecular and Cellular Biology
Volume34
Issue number12
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Zhang, Z. C., Liu, Y., Li, S. F., Guo, L., Zhao, Y., Qian, S. W., Wen, B., Tang, Q. Q., & Li, X. (2014). Suv39h1 mediates AP-2α-dependent inhibition of C/EBPα expression during adipogenesis. Molecular and Cellular Biology, 34(12), 2330-2338. https://doi.org/10.1128/MCB.00070-14