Transcriptional Activation of the Stearoyl-CoA Desaturase 2 Gene by Sterol Regulatory Element-binding Protein/Adipocyte Determination and Differentiation Factor 1

• Published in: The Journal of biological chemistry 1998-08, Vol.273 (34), p.22052-22058
• Main Authors: Tabor, David E., Kim, Jae B., Spiegelman, Bruce M., Edwards, Peter A.
• Format: Article
• Language: English
• Subjects: Animals; CCAAT-Enhancer-Binding Proteins; Cricetinae; DNA Footprinting; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Enzymologic; Helix-Loop-Helix Motifs; Isoenzymes - genetics; Mice; Nuclear Proteins - metabolism; Rats; RNA, Messenger - metabolism; Stearoyl-CoA Desaturase - genetics; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2; Transcription Factors - metabolism; Transcriptional Activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.34.22052

To identify genes that are transcriptionally activated by sterol regulatory element-binding proteins (SREBPs), we utilized mRNA differential display and mutant cells that express either high or low levels of transcriptionally active SREBP. This approach identified stearoyl-CoA desaturase 2 (SCD2) as a new SREBP-regulated gene. Cells were transiently transfected with reporter genes under the control of different fragments of the mouse SCD2 promoter. Constructs containing >199 base pairs of the SCD2 proximal promoter were activated following incubation of cells in sterol-depleted medium or as a result of co-expression of SREBP-1a, SREBP-2, or rat adipocyte determination and differentiation factor 1 (ADD1). Electromobility shift assays and DNase I footprint analysis demonstrated that recombinant SREBP-1a bound to a novel cis element (5′-AGCAGATTGTG-3′) in the proximal promoter of the SCD2 gene. The finding that the endogenous SCD2 mRNA levels were induced when wild-type Chinese hamster ovary fibroblasts were incubated in sterol-deficient medium is consistent with a role for SREBP in regulating transcription of the gene. These studies identify SCD2 as a new member of the family of genes that are transcriptionally regulated in response to changing levels of nuclear SREBP/ADD1. In addition, the sterol regulatory element in the SCD2 promoter is distinct from all previously characterized motifs that confer SREBP- and ADD1-dependent transcriptional activation.