Tissue-specific regulatory elements in the human alcohol dehydrogenase 6 gene

X. Zhi, E. M. Chan, H. J. Edenberg

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The human alcohol dehydrogenase gene ADH6 is expressed at the highest levels in fetal and adult liver. We have mapped cis-acting elements that affect its expression. The sequence from bp -234 to -262 (site C) that includes the TATA box was strongly bound by nuclear proteins from liver, hepatoma cells, and fibroblasts. A truncation that removed the upstream part of site C but left the TATA homology intact dramatically reduced transcription; altering 5 bp in this region had much less effect. Part of site C can be bound by C/EBPα, but cotransfection with C/EBPα or C/EBPβ did not stimulate transcription. The proximal region did not display tissue specificity, so we cloned the upstream region to search for additional regulatory sequences. The region between -21.6 and -22.3 kb stimulated transcription in hepatoma cells and inhibited it in fibroblasts. We identified two sites in this region that affect transcription independently of their orientation. Site 1 was a negative regulatory element in fibroblasts but had no effect in hepatoma cells. Site 2 was a positive regulatory element in hepatoma cells but had no effect in fibroblasts. This combination of positive and negative regulatory elements can play a significant role in the tissue-specific expression of ADH6.

Original languageEnglish (US)
Pages (from-to)487-497
Number of pages11
JournalDNA and Cell Biology
Volume19
Issue number8
DOIs
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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