Mouse Elovl-6 promoter is an SREBP target.
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.
Kumadaki
Shin
S
Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuda, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Matsuzaka
Takashi
T
Kato
Toyonori
T
Yahagi
Naoya
N
Yamamoto
Takashi
T
Okada
Sumiyo
S
Kobayashi
Kazuto
K
Takahashi
Akimitsu
A
Yatoh
Shigeru
S
Suzuki
Hiroaki
H
Yamada
Nobuhiro
N
Shimano
Hitoshi
H
D000123:Acetyltransferases / Q000235:genetics*; D000818:Animals; D000081031:Fatty Acid Elongases; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
C000630968:Elovl6 protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases