Mouse Elovl-6 promoter is an SREBP target

被引：94

作者：

Kumadaki, Shin ^{[1
]}

Matsuzaka, Takashi ^{[1
,2
]}

Kato, Toyonori ^{[1
]}

Yahagi, Naoya ^{[1
]}

Yamamoto, Takashi ^{[1
]}

Okada, Sumiyo ^{[1
]}

Kobayashi, Kazuto ^{[1
]}

Takahashi, Akimitsu ^{[1
]}

Yatoh, Shigeru ^{[1
]}

Suzuki, Hiroaki ^{[1
]}

Yamada, Nobuhiro ^{[1
]}

Shimano, Hitoshi ^{[1
,2
]}

机构：

[1] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Internal Med Endocrinol & Metab, Tsukuba, Ibaraki 3058575, Japan

[2] Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 3058575, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 368卷 / 02期

关键词：

fatty acids; elongase; sterol regulatory element-binding protein; lipogenic enzymes; transcription factor;

D O I：

10.1016/j.bbrc.2008.01.075

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：261 / 266

页数：6

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