The E-box like sterol regulatory element mediates the suppression of human Δ-6 desaturase gene by highly unsaturated fatty acids

• Published in: Biochemical and biophysical research communications 2002-08, Vol.296 (1), p.111-117
• Main Authors: Nara, Takayuki Y, He, Wei Song, Tang, Chongren, Clarke, Steven D, Nakamura, Manabu T
• Format: Article
• Language: English
• Subjects: Animals; Arachidonic acid; Base Sequence; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - physiology; Cell Line; DNA; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fatty Acid Desaturases - genetics; Fatty Acids, Unsaturated - pharmacology; Gene Expression Regulation, Enzymologic - drug effects; Genetic Vectors; Highly unsaturated fatty acids; Humans; Insulin; Linoleoyl-CoA Desaturase; Mice; Molecular Sequence Data; Phospholipids; Promoter Regions, Genetic; Sequence Homology, Amino Acid; Sterol regulatory element; Sterol regulatory element binding protein; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Transcriptional regulation; Δ-6 Desaturase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00851-3

Δ-6 Desaturase (D6D) catalyzes the first step of the synthesis of highly unsaturated fatty acids (HUFA) that play pivotal roles in many biological functions. The D6D expression is under feedback regulation by dietary HUFA. We co-transfected D6D promoter–reporter constructs to HepG2 cells with an expression vector of nuclear form sterol regulatory element binding protein-1c (SREBP-1c). A 90-bp region of the D6D promoter was required for the activation by SREBP-1c as well as for the suppression of the promoter activity by HUFA. The region contained two candidates of sterol regulatory element (SRE). Mutation analysis identified E-box like SRE (SRE-2) as essential for both SREBP-1c activation and HUFA suppression. SRE-2 has a core sequence of CAGCAG, and is also conserved in stearoyl CoA desatruases. Because HUFA are primarily incorporated into phospholipids (PL), our results suggest that the primary role of SREBP-1c in liver is the regulation of fatty acid supply for PL rather than for triglycerides.