Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-9-18
pubmed:databankReference
pubmed:abstractText
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/EBPalpha, but cotransfection with C/EBPalpha or C/EBPbeta 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-97
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10975466-Alcohol Dehydrogenase, pubmed-meshheading:10975466-Base Sequence, pubmed-meshheading:10975466-Binding Sites, pubmed-meshheading:10975466-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:10975466-DNA Footprinting, pubmed-meshheading:10975466-DNA-Binding Proteins, pubmed-meshheading:10975466-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10975466-Genomic Library, pubmed-meshheading:10975466-Humans, pubmed-meshheading:10975466-Molecular Sequence Data, pubmed-meshheading:10975466-Multigene Family, pubmed-meshheading:10975466-Mutagenesis, Site-Directed, pubmed-meshheading:10975466-Nuclear Proteins, pubmed-meshheading:10975466-Promoter Regions, Genetic, pubmed-meshheading:10975466-Protein Binding, pubmed-meshheading:10975466-Tissue Distribution, pubmed-meshheading:10975466-Transcription, Genetic
pubmed:year
2000
pubmed:articleTitle
Tissue-specific regulatory elements in the human alcohol dehydrogenase 6 gene.
pubmed:affiliation
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5122, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.