Mouse Elovl-6 promoter is an SREBP target
Mouse Elovl-6 promoter is an SREBP target
复制标题
DOI：
10.1016/j.bbrc.2008.01.075
复制
发表时间：
2008-04-04
影响因子：
3.1
通讯作者：
Shimano, Hitoshi
中科院分区：
文献类型：
--
作者：
Kumadaki, Shin;Matsuzaka, Takashi;Shimano, Hitoshi
Elovl-6是一种长脂肪酸延长酶，有助于脂肪酸的从头合成并调节肝脏胰岛素敏感性。不同营养条件下肝脏对Elovl-6基因表达的调节表明，与其他脂质酶基因一样，Elovl-6是调控脂肪酸合成的转录因子SREBP-1的靶标。支持的是，腺病毒RNAi敲低小鼠肝脏中SREBP-1可抑制Elovl-6 mRNA和脂肪酸合成酶水平。因此，我们分析了小鼠Elovl-6基因启动子，以确定其作为SREBP-1靶点的作用。HepG2细胞中小鼠Elovl-6基因的1.4 kb 5'侧区荧光素酶报告基因检测表明，核SREBP激活了Elovl-6启动子，突出了两个SREBP结合位点：近端SRE-1和远端SRE-2。EMSA结果表明，SRE-1对SREBP的亲和力高于SRE-2。ChIP实验证实肝核SREBP-1c蛋白在体内结合。这些数据表明，Elovl-6主要受SREBP-1c的直接调控。(C) 2008爱思唯尔公司版权所有。
Elovl-6, a long fatty acid elongase, contributes to de novo synthesis of fatty acids and regulates hepatic insulin sensitivity. Hepatic regulation of Elovl-6 gene expression in various nutritional conditions suggested that, like other lipogenic enzyme genes, Elovl-6 is a target of SREBP-1, a transcription factor governing fatty acid synthesis. Supportively, adenoviral RNAi knockdown of SREBP-1 in mouse liver suppressed Elovl-6 mRNA and fatty acid synthase levels. Therefore, we analyzed mouse Elovl-6 gene promoter to determine its role as an SREBP-1 target. Luciferase reporter assays of 1.4-kb 5' flanking region of mouse Elovl-6 gene in HepG2 cells demonstrated that nuclear SREBPs activated the Elovl-6 promoter, highlighting two SREBP binding sites: proximal SRE-1 and distal SRE-2. EMSA indicated that SRE-1 had higher affinity than SRE-2 for SREBP. ChIP assays confirmed in vivo binding of hepatic nuclear SREBP-1c protein. These data demonstrated that Elovl-6 is regulated directly and primarily by SREBP-1c. (C) 2008 Elsevier Inc. All rights reserved.