The E-box like sterol regulatory element mediates the suppression of human Delta-6 desaturase gene by highly unsaturated fatty acids.
Delta-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.
Nara
Takayuki Y
TY
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA.
He
Wei Song
WS
Tang
Chongren
C
Clarke
Steven D
SD
Nakamura
Manabu T
MT
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D044943:Fatty Acid Desaturases / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005822:Genetic Vectors; D006801:Humans; D050602:Linoleoyl-CoA Desaturase; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D004247:DNA; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase