Document Detail


GATA-2 and HNF-3beta regulate the human alcohol dehydrogenase 1A (ADH1A) gene.
MedLine Citation:
PMID:  16153155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Luke O Dannenberg; Hui-Ju Chen; Howard J Edenberg
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  DNA and cell biology     Volume:  24     ISSN:  1044-5498     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-12     Completed Date:  2006-02-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  543-52     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202, USA. edenberg@iupui.edu
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MeSH Terms
Descriptor/Qualifier:
Alcohol Dehydrogenase / genetics,  metabolism*
Cell Line
DNA Footprinting
Electrophoretic Mobility Shift Assay
GATA2 Transcription Factor / genetics,  metabolism*
Gene Expression Regulation*
Hepatocyte Nuclear Factor 3-beta / genetics,  metabolism*
Humans
Oligonucleotides
Regulatory Elements, Transcriptional / genetics
Grant Support
ID/Acronym/Agency:
R37AA06460/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/GATA2 Transcription Factor; 0/Oligonucleotides; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; EC 1.1.1.1/Alcohol Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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