Regulation of the rat SREBP-1c promoter in primary rat hepatocytes

Xiong Deng, Lauren M. Cagen, Henry G. Wilcox, Edwards Park, Rajendra Raghow, Marshall Elam

Research output: Contribution to journalArticle

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Abstract

We have cloned 5 kb of genomic DNA encompassing 1.72 kb of 5′-regulatory sequence and exons 1-c and 2 of the rat SREBP-1c gene. A 1.5-kb segment upstream from the transcription start site was ligated ahead of the luciferase reporter gene and tested for promoter activity by transient transfection assays in primary rat hepatocytes. We discovered that insulin strongly activated the full-length promoter, regardless of whether 5 or 20 mM glucose was in the culture medium during treatment. Stimulation by insulin was blocked by dibutyryl-cAMP and by polyunsaturated fatty acids, such as α-linolenic acid, γ-linolenic acid, or eicosapentaenoic acid; palmitic or oleic acids, however, had no inhibitory effect. A truncated promoter containing 149 bp of 5′ flanking DNA, including proximal NF-Y, E-box, SRE, and Sp1 sites, retained most of the response. This is the first report that insulin, cAMP, and polyunsaturated fatty acids modulate the proximal SREBP-1c promoter in rat hepatocytes mirroring physiological regulation of SREBP-1c in vivo.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number1
DOIs
StatePublished - Jan 11 2002

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Sterol Regulatory Element Binding Protein 1
Rats
Hepatocytes
alpha-Linolenic Acid
Insulin
Unsaturated Fatty Acids
Genes
Palmitic Acids
Oleic Acids
Eicosapentaenoic Acid
Transcription Initiation Site
DNA
Luciferases
Reporter Genes
Transfection
Culture Media
Exons
Assays
Glucose

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Regulation of the rat SREBP-1c promoter in primary rat hepatocytes. / Deng, Xiong; Cagen, Lauren M.; Wilcox, Henry G.; Park, Edwards; Raghow, Rajendra; Elam, Marshall.

In: Biochemical and Biophysical Research Communications, Vol. 290, No. 1, 11.01.2002, p. 256-262.

Research output: Contribution to journalArticle

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