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Cloning and Characterization of the Human Stearoyl-CoA Desaturase Gene Promoter: Transcriptional Activation by Sterol Regulatory Element Binding Protein and Repression by Polyunsaturated Fatty Acids and Cholesterol

https://doi.org/10.1006/bbrc.2001.5102Get rights and content

Abstract

Stearoyl-CoA desaturase (SCD) is a microsomal enzyme required for the biosynthesis of oleate (C18:1) and palmitoleate (C16:1) which are the major monounsaturated fatty acids of membrane phospholipids, triglycerides and cholesterol esters. Previously the full-length human skin cDNA was sequenced and the exon and intron structure of the single functional SCD gene determined. Here we report on the cloning and characterization of the promoter region of the human SCD gene. The human promoter structure is very similar to that of the mouse SCD1 isoform and contains conserved regulatory sequences for the binding of several transcription factors including the sterol regulatory element binding protein (SREBP), CCAAT enhancer binding protein-alpha (C/EBPα) and nuclear factor-1 (NF-1) that have been shown to transactivate the transcription of the mouse SCD1 gene. Polyunsaturated fatty acids and cholesterol decreased the SCD promoter-luciferase activity when transiently transfected into HepG2 cells. The decrease in promoter activity correlated with decreases in endogenous SCD mRNA and protein levels. Cotransfection experiment in HepG2 cells showed transactivation of the SCD promoter-luciferase activity by an expression vector containing SREBP-1a and 1c. Our studies indicate that the transcription of the human SCD gene is repressed by polyunsaturated fatty acids and cholesterol and that SREBP plays a role in the transcriptional activation of this gene.

References (25)

  • H.G. Enoch et al.

    J. Biol. Chem.

    (1976)
  • J.M. Ntambi

    Prog. Lipid. Res.

    (1995)
  • R. Kasturi et al.

    J. Biol. Chem.

    (1982)
  • J.M. Ntambi et al.

    J. Biol. Chem.

    (1988)
  • K.H. Kaestner et al.

    J. Biol. Chem.

    (1989)
  • M. Singh et al.

    Biochim. Biophys. Acta

    (1998)
  • D.E. Tabor et al.

    J. Biol. Chem.

    (1999)
  • D.E. Tabor et al.

    J. Biol. Chem.

    (1998)
  • J. Pai et al.

    J. Biol. Chem.

    (1998)
  • I. Shimomura et al.

    J. Biol. Chem.

    (1998)
  • N. Yahagi et al.

    J. Biol. Chem.

    (1999)
  • T.S. Worgall et al.

    J. Biol. Chem.

    (1998)
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    Abbreviations used: SCD, stearoyl-CoA desaturase; SREBP, sterol regulatory element binding protein; PUFA, polyunsaturated fatty acid; AA, arachidonic acid; DHA, decosahexaenoic acid; EPA, ecosapentenoic acid; LA, linoleic acid.

    1

    To whom correspondence should be addressed at Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706. Fax: 608-265-3272. E-mail: [email protected].

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