title: Identification of human ELOVL5 enhancer regions controlled by SREBP.
abstract: Fatty acid elongase 5 (ELOVL5) is an enzyme involved in the synthesis of polyunsaturated fatty acids. Sterol Regulatory Element-binding Protein (SREBP)-1 activates ELOVL5 and increases polyunsaturated fatty acid synthesis, which in turn negatively affects SREBP-1 expression. Thus, ELOVL5 has been established as an SREBP-1 target gene and an important component of the negative feedback loop of de novo lipogenesis. However, the human ELOVL5 promoter/enhancer has not been fully analyzed and the location of SREBP biding sites around the ELOVL5 gene has yet to be defined. Here we performed a detailed promoter/enhancer analysis of human ELOVL5 gene, and identified two new SREBP binding sites, one in the 10 kb upstream region and one in the exon 1. These two SRE motifs are conserved among mammals and the mechanism found in the present study by which SREBP activates ELOVL5 is considered to be common in mammals. Through these findings, we clarified the molecular mechanism how SREBP activates ELOVL5, an important regulator of de novo lipogenesis.
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Akito
authors: A
authors: Shikama
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Haruna
authors: H
authors: Shinozaki
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Yoshinori
authors: Y
authors: Takeuchi
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Takashi
authors: T
authors: Matsuzaka
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Yuichi
authors: Y
authors: Aita
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Tomoki
authors: T
authors: Murayama
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Yoshikazu
authors: Y
authors: Sawada
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Xiaoying
authors: X
authors: Piao
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Naoki
authors: N
authors: Toya
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Yukari
authors: Y
authors: Oya
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Ayako
authors: A
authors: Takarada
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Yukari
authors: Y
authors: Masuda
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Makiko
authors: M
authors: Nishi
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Midori
authors: M
authors: Kubota
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
authors: Yoshihiko
authors: Y
authors: Izumida
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Yoshimi
authors: Y
authors: Nakagawa
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Hitoshi
authors: H
authors: Iwasaki
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Kazuto
authors: K
authors: Kobayashi
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Shigeru
authors: S
authors: Yatoh
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Hiroaki
authors: H
authors: Suzuki
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Hiroaki
authors: H
authors: Yagyu
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Yasushi
authors: Y
authors: Kawakami
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Nobuhiro
authors: N
authors: Yamada
authors: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
authors: Hitoshi
authors: H
authors: Shimano
authors: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan. Electronic address: nyahagi-tky@umin.ac.jp.
authors: Naoya
authors: N
authors: Yahagi
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005091:Exons; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C000630954:ELOVL5 protein, human; D005231:Fatty Acids, Unsaturated; D011994:Recombinant Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
keywords: Fatty acid synthesis; Polyunsaturated fatty acids; Transcription