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 F. Osborne

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Sterol regulation of fatty acid synthase promoter: Coordinate feedback regulation of two major lipid pathways'. Together they form a unique fingerprint.

Cite this