Sterol regulation of fatty acid synthase promoter: Coordinate feedback regulation of two major lipid pathways

Mary K. Bennett, Jose M. Lopez, Hugo B. Sanchez, Timothy Osborne

Research output: Contribution to journalArticle

Abstract

The gene encoding fatty acid synthase, the essential multi-functional enzyme of fatty acid biosynthesis, is shown to be regulated by cellular sterol levels similar to genes that encode important proteins of cholesterol metabolism. We show that expression of the endogenous FAS gene is repressed when regulatory sterols are included in the culture medium of HepG2 cells and that the FAS promoter is subject to similar regulation when fused to the luciferase reporter gene. Mutational studies demonstrate that sterol regulation is mediated by binding sites for the sterol regulatory element-binding protein (SREBP) and transcription factor Sp1, making it mechanistically similar to sterol regulation of the low density lipoprotein receptor gene. It is also demonstrated that SREBP and Sp1 synergistically activate the FAS promoter in Drosophila tissue culture cells, which lack endogenous Sp1. These experiments provide key molecular evidence that directly links the metabolism of fatty acids and cholesterol together.

Original languageEnglish (US)
Pages (from-to)25578-25583
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number43
DOIs
StatePublished - Oct 27 1995
Externally publishedYes

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Fatty Acid Synthases
Sterols
Genes
Sterol Regulatory Element Binding Proteins
Feedback
Lipids
Metabolism
Fatty Acids
Cholesterol
Sp1 Transcription Factor
Tissue culture
Gene encoding
LDL Receptors
Biosynthesis
Hep G2 Cells
Luciferases
Reporter Genes
Drosophila
Culture Media
Cell Culture Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sterol regulation of fatty acid synthase promoter : Coordinate feedback regulation of two major lipid pathways. / Bennett, Mary K.; Lopez, Jose M.; Sanchez, Hugo B.; Osborne, Timothy.

In: Journal of Biological Chemistry, Vol. 270, No. 43, 27.10.1995, p. 25578-25583.

Research output: Contribution to journalArticle

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