Stearoyl-CoA desaturase is the rate-limiting enzyme in the production of mono-unsaturated fatty acids. We have recently cloned and characterized the human Scd cDNA and SCD (the stearoyl-CoA desaturase structural gene) on chromosome 10, as well as the non-transcribed pseudogene on chromosome 17. In order to further define SCD regulation and function, we have isolated and characterized the promoter of the structural gene. Screening of chromosome-10-specific libraries resulted in the isolation of 4.1kb of SCD sequence upstream of the translation start site. Binding sites for transcription factors critical for mouse Scd1 and Scd2 promoter activity, such as sterol-regulated-element-binding protein and nuclear factor Y, were present in the human SCD promoter (Scd is the mouse stearoyl-CoA desaturase gene). Deletion analysis in HaCaT keratinocytes identified a critical region for promoter activity between nts 496–609 upstream of the translation start site. Site-directed mutagenesis of binding sites in this region identified the CCAAT box as the critical cis-element for SCD promoter activity. An electrophoretic mobility-shift assay confirmed that this element binds nuclear proteins from HaCaT keratinocytes. The polyunsaturated-fatty-acid (PUFA) response element, previously identified in the promoters of mouse Scd1 and Scd2, was found to be conserved in the human SCD promoter, and contained the critical CCAAT cis-element. A minimal promoter construct including this region was responsive to fatty acids, with oleate and linoleate decreasing transcription and stearate increasing it. These studies indicate that CCAAT-box-binding proteins activate SCD transcription in cultured keratinocytes and that fatty acids modulate transcription, most likely through the conserved PUFA response element.
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July 2001
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Research Article|
June 25 2001
Isolation and characterization of the human stearoyl-CoA desaturase gene promoter: requirement of a conserved CCAAT cis-element
Lin ZHANG;
Lin ZHANG
1
∗Skin Biology Technical Resourse Center, Johnson and Johnson, Consumer Products World Wide, 199 Grandview Road, Skillman, NJ 08558 U.S.A.
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Lan GE;
Lan GE
∗Skin Biology Technical Resourse Center, Johnson and Johnson, Consumer Products World Wide, 199 Grandview Road, Skillman, NJ 08558 U.S.A.
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Tai TRAN;
Tai TRAN
2
∗Skin Biology Technical Resourse Center, Johnson and Johnson, Consumer Products World Wide, 199 Grandview Road, Skillman, NJ 08558 U.S.A.
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Kurt STENN;
Kurt STENN
∗Skin Biology Technical Resourse Center, Johnson and Johnson, Consumer Products World Wide, 199 Grandview Road, Skillman, NJ 08558 U.S.A.
†Juvenir Biosciences, 199 Grandview Road, Johnson and Johnson, Consumer Products World Wide, Skillman, NJ 08558, U.S.A.
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Stephen M. PROUTY
Stephen M. PROUTY
3
∗Skin Biology Technical Resourse Center, Johnson and Johnson, Consumer Products World Wide, 199 Grandview Road, Skillman, NJ 08558 U.S.A.
3To whom correspondence should be sent, at present address: Drug Discovery, R. W. Johnson Pharmaceutical Research Institute, Welsh & McKean Roads, P. O. Box 776, Spring House, PA 19477, U.S.A. (e-mail sprouty1@prius.jnj.com).
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Publisher: Portland Press Ltd
Received:
February 28 2001
Revision Received:
April 02 2001
Accepted:
May 10 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 357 (1): 183–193.
Article history
Received:
February 28 2001
Revision Received:
April 02 2001
Accepted:
May 10 2001
Citation
Lin ZHANG, Lan GE, Tai TRAN, Kurt STENN, Stephen M. PROUTY; Isolation and characterization of the human stearoyl-CoA desaturase gene promoter: requirement of a conserved CCAAT cis-element. Biochem J 1 July 2001; 357 (1): 183–193. doi: https://doi.org/10.1042/bj3570183
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