Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specificity protein 1 (Sp1)

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

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The induction of genes involved in lipid biosynthesis by insulin is mediated in part by the sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c is directly regulated by insulin by transcriptional and post-transcriptional mechanisms. Previously, we have demonstrated that the insulin-responsive cis-acting unit of the rat SREBP-1c promoter is composed of several elements that include a sterol regulatory element, two liver X receptor elements, and a number of conserved GC boxes. Here we systematically dissected the role of these GC boxes and report that five bona fide Sp1-binding elements of the SREBP-1c promoter determine its basal and insulin-induced activation. Luciferase expression driven by the rat SREBP-1c promoter was accelerated by ectopic expression of Sp1, and insulin further enhanced the transactivation potential of Sp1. Introduction of a small interfering RNA against Sp1 reduced both basal and insulin-induced activation of the SREBP-1c promoter. We also found that Sp1 interacted with both SREBP-1c and LXRα proteins and that insulin promoted these interactions. Chromatin immunoprecipitation studies revealed that insulin facilitated the recruitment of the steroid receptor coactivator-1 to the SREBP-1c promoter. These studies identify a novel mechanism by which maximal activation of the rat SREBP-1c gene expression by insulin is mediated by Sp1 and its enhanced ability to interact with other transcriptional regulatory proteins.

Original languageEnglish (US)
Pages (from-to)17517-17529
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number24
DOIs
StatePublished - Jun 15 2007

Fingerprint

Sterol Regulatory Element Binding Protein 1
Rats
Genes
Insulin
Proteins
Chemical activation
Nuclear Receptor Coactivator 1
Chromatin Immunoprecipitation
Biosynthesis
Sterols
Luciferases
Protein Binding
Gene expression
Liver
Small Interfering RNA
Transcriptional Activation
Chromatin
Lipids
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specificity protein 1 (Sp1). / Deng, Xiong; Yellaturu, Chandrahasa; Cagen, Lauren; Wilcox, Henry G.; Park, Edwards; Raghow, Rajendra; Elam, Marshall.

In: Journal of Biological Chemistry, Vol. 282, No. 24, 15.06.2007, p. 17517-17529.

Research output: Contribution to journalArticle

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