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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-9-12
pubmed:abstractText
In this paper, we have identified several distal cis-acting elements that contribute to the regulation and tissue- specificity of ADH1A, which encodes an alcohol dehydrogenase (ADH) that metabolizes ethanol. A negative element from bp -1873 to -1558, relative to the translational start site, decreased transcriptional activity to 52% in H4IIE-C3 cells and 70% in CV-1 cells. A positive element from bp -2459 to -2173 increased transcriptional activity twofold in H4IIE-C3 cells and 1.7-fold in CV-1 cells. Gel mobility shift and supershift assays demonstrated that GATA-2 bound a region within this positive element. A tissue-specific regulatory element from bp -6380 to -5403 increased transcription twofold in H4IIE-C3 cells while decreasing transcription to 86% in CV-1 cells. Within this tissue-specific fragment, the region from bp -5668 to -5403 increased transcription 1.7-fold in H4IIE-C3 cells and 1.3-fold in CV-1 cells. Hepatocyte nuclear factor-3beta (HNF- 3beta) bound a region of the tissue-specific element in CV-1 cells, but not in H4IIE-C3 cells. Positive regulation of the ADH1A gene may be influenced by GATA-2 binding, while differences in HNF-3beta binding in cells/tissues may contribute to tissue specificity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
543-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
GATA-2 and HNF-3beta regulate the human alcohol dehydrogenase 1A (ADH1A) gene.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202, USA. edenberg@iupui.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural