Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate control of cellular lipid.
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.
Lopez
J M
JM
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717, USA.
Bennett
M K
MK
Sanchez
H B
HB
Rosenfeld
J M
JM
Osborne
T F
TF
D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003001:Cloning, Molecular; D018983:DNA Footprinting; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I; D005227:Fatty Acids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D018257:Helix-Loop-Helix Motifs; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1; D013261:Sterols / Q000096:biosynthesis*; D016385:TATA Box; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C497387:SREBF1 protein, human; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D013261:Sterols; D014157:Transcription Factors; D002784:Cholesterol; D003850:Deoxyribonuclease I; D000103:Acetyl-CoA Carboxylase