NF-Y has a novel role in sterol-dependent transcription of two cholesterogenic genes

Simon M. Jackson, Johan Ericsson, Timothy F. Osborne, Peter A. Edwards

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21445-21448
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number37
DOIs
StatePublished - Sep 15 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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