Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cell Res. 2010 Apr;20(4):470-9. doi: 10.1038/cr.2010.24. Epub 2010 Feb 16.
SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein alpha (C/EBPalpha) during adipocyte differentiation. C/EBPalpha, but not C/EBPalphap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPalpha upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPalpha upregulated SIRT1 protein level and knockdown of C/EBPalpha led to the decrease of SIRT1 protein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPalpha bound to the SIRT1 promoter at a consensus C/EBPalpha binding site. These data demonstrate that C/EBPalpha regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.
SIRT1 在脂肪生成中发挥着重要作用，但 SIRT1 如何在脂肪生成中被调控在很大程度上仍是未知的。在本研究中，我们发现随着脂肪细胞分化，SIRT1 蛋白和 mRNA 水平均升高。C/EBPα（而非 C/EBPαp30）可在 HeLa 细胞和 3T3-L1 前脂肪细胞中激活 SIRT1 启动子。此外，C/EBPα 可在上皮细胞和 Soas2 细胞中上调 SIRT1 mRNA 和蛋白水平，且以 p53 非依赖的方式增加 SIRT1 的表达。在前脂肪细胞中，C/EBPα 的异位表达可上调 SIRT1 蛋白水平，而 C/EBPα 的敲低则导致 SIRT1 蛋白水平下降。此外，通过启动子缺失分析、凝胶阻滞实验和染色质免疫沉淀实验，我们发现 C/EBPα 可在一个公认的 C/EBPα 结合位点上结合 SIRT1 启动子。这些数据表明，C/EBPα 通过直接结合 SIRT1 启动子在脂肪生成过程中调控 SIRT1 的表达。
