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  • Title: Mouse Elovl-6 promoter is an SREBP target.
    Author: Kumadaki S, Matsuzaka T, Kato T, Yahagi N, Yamamoto T, Okada S, Kobayashi K, Takahashi A, Yatoh S, Suzuki H, Yamada N, Shimano H.
    Journal: Biochem Biophys Res Commun; 2008 Apr 04; 368(2):261-6. PubMed ID: 18226595.
    Abstract:
    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.
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