Abstract
The 5'-flanking region of the gene for hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is shown to contain promoter sequences that drive transcription in vitro in the presence of a HeLa whole-cell extract. DNase I protection studies revealed at least six different regions within the 277-base-pair (bp) promoter that bind nuclear proteins and produce 'footprints'. The functional significance of these sequences was determined through transcriptional analysis of a series of substitution mutations that scrambled short sequences throughout this region. Two of the footprint sequences were crucial for transcription in vitro; one of these contains a match in 6 of 6 bp, with a sequence in the adenovirus type 2 major late promoter that is known to be required for transcription. Scrambling a 26-bp sequence in a third footprint led to a consistent 2-fold increase in transcription, suggesting that this sequence might be a site for negative regulation. These studies define three regions that play a role in regulating transcription of the gene for HMG-CoA reductase, a negatively regulated enzyme in the cholesterol biosynthetic pathway.
Original language | English (US) |
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Pages (from-to) | 3614-3618 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 84 |
Issue number | 11 |
DOIs | |
State | Published - 1987 |
ASJC Scopus subject areas
- General