Regulation of human alcohol dehydrogenase gene ADH7: Importance of an AP-1 site

Shailaja Kotagiri, Howard J. Edenberg

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Abstract

The structure and function of the human alcohol dehydrogenase 7 (ADH7) promoter were analyzed. A promoter fragment extending to bp -232 functioned well in H4IIE-C3, CV-1, and HeLa cells, whereas the region extending further upstream to bp -799 had no significant effect on activity. We identified cis- acting elements in the proximal 232 bp and examined their effect on promoter activity. Mutation of site A, where c-Jun bound, caused a drastic decrease in the promoter activity in H4IIE-C3 and CV-1 cells, suggesting that AP-1 plays an important role in the regulation of ADH7. Mutation of site B also caused a large drop in promoter activity in both cell lines; C/EBPα can bind to this site, but because the site affects activity approximately equally in CV-1 cells that lack C/EBPα and in H4IIE-C3 cells that contain low levels, other proteins are likely to play the major roles in vivo. Mutation of site C, where C/EBP bound and c-Jun bound weakly, had different effects in the two cell lines: in H4IIE-c3 cells, the site C mutation did not significantly increase promoter activity, whereas in CV-1 cells, which lack C/EBPα, it led to a doubling of activity. Surprisingly, cotransfection of the wild-type promoter with C/EBPα or C/EBPβ led to a decrease in promoter activity, which might in part explain the lack of activity of ADH7 in adult liver.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalDNA and Cell Biology
Volume17
Issue number7
DOIs
StatePublished - Jan 1 1998

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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