NF-Y has a novel role in sterol-dependent transcription of two cholesterogenic genes.
The transcription of farnesyl diphosphate (FPP) synthase is regulated up to 30-fold by the sterol status of the cell. Point mutations in a 6-base pair ATTGGC sequence in the promoter disrupt both sterol-dependent transcription in vivo as well as binding of the transcription factor NF-Y in vitro. Co-transfection of cells with NF-YA29, a dominant negative form of NF-Y, and various promoter-reporter genes specifically inhibits the sterol-dependent regulation of FPP synthase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase. In contrast, NF-YA29 does not affect the regulation of reporter genes under the control of promoters derived from either the HMG-CoA reductase or the low density lipoprotein receptor gene. Transient expression of the 68-kDa transcriptionally active fragment of sterol regulatory element-binding protein in cells stimulates an HMG-CoA synthase-reporter gene over 90-fold. This induction is blocked in cells co-expressing NF-YA29. We hypothesize that NF-Y plays a novel role in sterol-dependent regulation of two key genes in the cholesterol biosynthetic pathway and that this role requires a specific interaction with the sterol regulatory element-binding protein or related transcription factors.
Jackson
S M
SM
Department of Biological Chemistry, UCLA 90024, USA.
Ericsson
J
J
Osborne
T F
TF
Edwards
P A
PA
D019883:Alkyl and Aryl Transferases; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D016466:CHO Cells; D002784:Cholesterol / Q000096:biosynthesis; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051228:Geranyltranstransferase; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000096:biosynthesis*; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014166:Transferases / Q000096:biosynthesis*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D002784:Cholesterol; D008156:Luciferases; D014166:Transferases; D006904:Hydroxymethylglutaryl-CoA Synthase; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase