Document Detail

Tissue-specific differences in the expression of the human ADH2 alcohol dehydrogenase gene and in binding of factors to cis-acting elements in its promoter.
MedLine Citation:
PMID:  8172654     Owner:  NLM     Status:  MEDLINE    
The human alcohol dehydrogenase gene ADH2 is expressed at high levels in liver, at lower levels in kidney and several other tissues, and is not expressed in other tissues such as spleen. This pattern of expression suggests a complex regulatory region that responds to a variety of transcription factors in different cellular contexts. Seven cis-acting sequences in the proximal 271 bp of the ADH2 promoter were mapped. The occupancy of these sites differed markedly among extracts from liver, kidney, spleen, H4IIE-C3 cells, HeLa cells, and CV-1 cells. These differences in occupancy were accompanied by differences in gene expression in the three cell lines. The ADH2 promoter directed substantial CAT expression in H4IIE-C3 cells (rat hepatoma) and in HeLa cells, but only minimal expression in CV-1 cells (monkey kidney fibroblasts). The three cell lines differed in the effects of deletions within the promoter. An ADH2 promoter that contained both the USF/MLTF site and the G3T site gave four- to eight-fold higher expression in both H4IIE-C3 and HeLa cells than a smaller promoter that lacked these sites; in contrast, these sequences did not significantly stimulate transcription in CV-1 cells. A CTF/NF-I-related site acted as a negative element in all three cell lines. Coexpression of C/EBP alpha altered the cell specificity. The ADH2 promoter was moderately stimulated (two-fold) by coexpression of C/EBP alpha in H4IIE-C3 cells, but markedly stimulated in HeLa cells and in CV-1 cells (11- and 20-fold, respectively). These results demonstrate the differential importance of cis-acting sequences and of specific transcription factors in different cells, which allows regulated expression of ADH2 in multiple tissues.
C J Brown; L Zhang; H J Edenberg
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  DNA and cell biology     Volume:  13     ISSN:  1044-5498     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-06-06     Completed Date:  1994-06-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  235-47     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202-5122.
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MeSH Terms
Alcohol Dehydrogenase / biosynthesis*,  genetics*
Base Sequence
Binding Sites
Cell Line
Cell Nucleus / metabolism
Cercopithecus aethiops
Cloning, Molecular
DNA / metabolism*
DNA-Binding Proteins / metabolism*
Deoxyribonuclease I
Gene Expression Regulation, Enzymologic*
Hela Cells
Kidney / enzymology
Liver / enzymology
Molecular Sequence Data
Organ Specificity
Promoter Regions, Genetic*
Spleen / enzymology
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Oligodeoxyribonucleotides; 9007-49-2/DNA; EC Dehydrogenase; EC I

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