5′ end of hmg CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription

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Abstract

Cholesterol homeostasis is maintained by feedback inhibition of transcription of the gene encoding HMG CoA reductase. To study this mechanism, we joined the 5′ end of the hamster reductase gene to the coding region for chloramphenicol acetyltransferase (CAT). The chimeric gene produced high levels of CAT activity in mouse L cells; sterols suppressed expression by 70% to 90%. Sequences responsible for both promotion and inhibition of transcription were distributed over 500 by extending 300 by upstream of the reductase transcription initiation sites. Any sizable deletion within this region decreased CAT expression in vivo and CAT mRNA transcription in vitro. This region contains five hexanucleotide repeats (CCGCCC or GGGCGG) that occur in promoters of viral and cellular housekeeping genes. Every reductase-CAT plasmid that showed transcriptional activity also showed inhibition by sterols, indicating that the sites for promotion and inhibition of transcription are closely associated.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalCell
Volume42
Issue number1
DOIs
StatePublished - 1985

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Chloramphenicol O-Acetyltransferase
Coenzyme A
Transcription
Oxidoreductases
Genes
Cholesterol
Sterols
Hydroxymethylglutaryl CoA Reductases
Gene encoding
Transcription Initiation Site
Essential Genes
Cricetinae
Plasmids
Homeostasis
Feedback
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

5′ end of hmg CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription. / Osborne, Timothy F.; Goldstein, Joseph L.; Brown, Michael S.

In: Cell, Vol. 42, No. 1, 1985, p. 203-212.

Research output: Contribution to journalArticle

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