Abstract
Transcription from the housekeeping promoter for the acetyl coenzyme A carboxylase (ACC) gene, which encodes the rate-controlling enzyme of fatty acid biosynthesis, is shown to be regulated by cellular sterol levels through novel binding sites for the sterol-sensitive sterol regulatory element binding protein (SREBP)-1 transcription factor. The position of the SREBP sites relative to those for the ubiquitous auxiliary transcription factor Sp1 is reminiscent of that previously described for the sterol-regulated low density lipoprotein receptor promoter. The experiments provide molecular evidence that the metabolism of fatty acids and cholesterol, two different classes of essential cellular lipids, are coordinately regulated by cellular lipid levels.
MeSH Terms
Acetyl-CoA Carboxylase/biosynthesis,genetics
Animals
Base Sequence
Binding Sites
CCAAT-Enhancer-Binding Proteins
Cell Line
Cholesterol/metabolism
Cloning, Molecular
DNA Footprinting
DNA, Complementary
DNA-Binding Proteins/metabolism
Deoxyribonuclease I
Fatty Acids/metabolism
Gene Expression Regulation, Enzymologic
Helix-Loop-Helix Motifs
Homeostasis
Humans
Kinetics
Lipid Metabolism
Molecular Sequence Data
Nuclear Proteins/metabolism
Polymerase Chain Reaction
Promoter Regions, Genetic
Rats
Recombinant Proteins/biosynthesis
Sterol Regulatory Element Binding Protein 1
Sterols/biosynthesis
TATA Box
Transcription Factors/metabolism
Transcription, Genetic
Transfection
Tumor Cells, Cultured
Chemicals
CCAAT-Enhancer-Binding Proteins
DNA, Complementary
DNA-Binding Proteins
Fatty Acids
Nuclear Proteins
Recombinant Proteins
SREBF1 protein, human
Srebf1 protein, rat
Sterol Regulatory Element Binding Protein 1
Sterols
Transcription Factors
Cholesterol
Deoxyribonuclease I
Acetyl-CoA Carboxylase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lopez J M
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717, USA.
Bennett M K
Sanchez H B
Rosenfeld J M
Osborne T F
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