A novel c.-274C>G polymorphism in bovine SIRT1 gene contributes to diminished promoter activity and is associated with increased body size
A novel c.-274C>G polymorphism in bovine SIRT1 gene contributes to diminished promoter activity and is associated with increased body size
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DOI：
10.1111/age.12048
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发表时间：
2013-08-01
期刊：
影响因子：
2.4
通讯作者：
Chen, Hong
中科院分区：
文献类型：
--
作者：
Li, Ming-xun;Sun, Xiao-mei;Chen, Hong
SIRT1 是酵母沉默信息调节因子 2 (SIR2) 的哺乳动物同源物，是一种 NAD(+) 依赖性脱乙酰酶，属于 III 类组蛋白脱乙酰酶。它在多种细胞过程中发挥着重要作用，包括抗应激、线粒体功能、炎症抑制和 DNA 修复。在本研究中，我们筛选并鉴定了SIRT1启动子区域中的一个新的多态性（c.-274C>G）。计算机预测表明，该 SNP 位于细胞周期依赖性元件 (CDE) 结合基序的核心。有趣的是，G 等位基因废除了 CDE 结合位点，这表明了其功能意义。在荧光素酶检测系统中，我们发现与 C 等位基因相比，含有 G 等位基因的构建体表现出显着较低的启动子活性，这可能会下调 SIRT1 的表达水平。此外，我们观察到南阳牛的c.-274C>G多态性与生长性状之间存在显着相关性，这表明基于异常转录因子的SIRT1抑制可能会增加牛的脂肪量和体型。
SIRT1, a mammalian homologue for yeast silent information regulator 2 (SIR2), is a NAD(+)-dependent deacetylase that belongs to the class III histone deacetylases. It plays an important role in diverse cellular processes, including stress resistance, mitochondrial function, suppression of inflammation and DNA repair. In this study, we screened and identified a novel polymorphism (c.-274C>G) in the SIRT1 promoter region. In silico prediction reveals that this SNP is in the core of cell cycle-dependent element (CDE)-binding motif. Interestingly, the G allele abolished a CDE-binding site, which suggested its functional significance. In the luciferase assay system, we found that the G allele-containing construct displayed a strikingly lower promoter activity compared with the C allele, which may downregulate SIRT1 expression levels. Additionally, we observed a significant association between the c.-274C>G polymorphism and growth traits in Nanyang cattle, suggesting that anomalous transcription factor-based repression of SIRT1 may increase bovine fat mass and body size.