TITLE

Tissue-Specific Regulatory Elements in the Human Alcohol Dehydrogenase 6 Gene

AUTHOR(S)
Zhi, Xin; Chan, Edward M.; Edenberg, Howard J.
PUB. DATE
August 2000
SOURCE
DNA & Cell Biology;Aug2000, Vol. 19 Issue 8, p487
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 -34 to -62 (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/EBPa, but cotransfection with C/EBPa or C/EBP� 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 -1.6 and -2.3 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.
ACCESSION #
5322754

 

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