Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
Mol Biol Rep. 2012 Oct;39(10):9445-51. doi: 10.1007/s11033-012-1809-3. Epub 2012 Jun 28.
It was recently reported that C1qTNF-related protein 5 (CTRP5) regulates glucose and lipid metabolism in muscle cells. However, the molecular mechanism of CTRP5 expression has not been fully investigated. In this study we demonstrate the mechanism regulating the transcription of the CTRP5 gene in muscle cells. We found that potential binding sites for transcription factors were conserved in proximal region of CTRP5 promoters in human, mouse and rat. Among these factors, Ets-2 was found to increase the promoter activity of the CTRP5 gene in C2C12 cells. Deletion of -166 to -80 in the CTRP5 promoter region significantly decreased Ets-2-induced CTRP5 promoter activity. Mutagenesis evaluation indicated that two putative Ets-2-binding sites in the CTRP5 promoter are important in CTRP5 activation. Promoter enzyme immunoassay showed that Ets-2 binds directly to two Ets-2-responsive elements at regions -166/-80 of the CTRP5 promoter. Taken together, these results suggest that Ets-2 play a key role in transcriptional regulation of CTRP5 in muscle cells.
最近有报道称，C1qTNF 相关蛋白 5（CTRP5）可调节肌肉细胞中的葡萄糖和脂质代谢。然而，CTRP5 表达的分子机制尚未完全研究清楚。在本研究中，我们证明了调节肌肉细胞中 CTRP5 基因转录的机制。我们发现，在人类、小鼠和大鼠的 CTRP5 启动子近端区域，存在转录因子的潜在结合位点。在这些因子中，Ets-2 被发现可增加 C2C12 细胞中 CTRP5 基因的启动子活性。CTRP5 启动子区域-166 至-80 缺失显著降低了 Ets-2 诱导的 CTRP5 启动子活性。突变评估表明，CTRP5 启动子中的两个假定 Ets-2 结合位点在 CTRP5 激活中很重要。启动子酶免疫测定显示，Ets-2 直接结合于 CTRP5 启动子区域-166/-80 处的两个 Ets-2 反应元件。综上所述，这些结果表明 Ets-2 在肌肉细胞中 CTREP5 的转录调控中发挥关键作用。
