Identification of human ELOVL5 enhancer regions controlled by SREBP

Akito Shikama, Haruna Shinozaki, Yoshinori Takeuchi, Takashi Matsuzaka, Yuichi Aita, Tomoki Murayama, Yoshikazu Sawada, Xiaoying Piao, Naoki Toya, Yukari Oya, Ayako Takarada, Yukari Masuda, Makiko Nishi, Midori Kubota, Yoshihiko Izumida, Yoshimi Nakagawa, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki SuzukiHiroaki Yagyu, Yasushi Kawakami, Nobuhiro Yamada, Hitoshi Shimano, Naoya Yahagi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)857-863
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume465
Issue number4
DOIs
StatePublished - 2015/10/02

Keywords

  • Fatty acid synthesis
  • Polyunsaturated fatty acids
  • Transcription

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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