| HNF3beta and GATA-4 transactivate the liver-enriched homeobox gene, Hex. | |
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MedLine Citation:
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PMID: 10767553 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The orphan homeobox gene, Hex, has a limited domain of expression which includes the developing and adult mouse liver. Hex is expressed in the developing liver coincident with the forkhead/winged helix transcription factor, Hepatocyte Nuclear Factor 3beta (HNF3beta). Although preliminary characterization of the mouse Hex promoter has recently been reported, the identity of the molecular regulators that drive liver expression is not known. We hypothesized that putative HNF3beta and GATA-4 elements within the Hex promoter would confer liver-enriched expression. A series of Hex promoter-driven luciferase reporter constructs were transfected in liver-derived HepG2 and fibroblast-like Cos cells+/-HNF3beta or GATA expression plasmids. The Hex promoter region from nt -235/+22 conferred basal activity in both HepG2 and Cos cells, with the region from -103/+22 conferring liver-enriched activity. HNF3beta and GATA-4 transactivated the promoter via response elements located within nt -103/+22, whereas Sp1 activated the -235/+22 construct. Mutation of the HNF3 element significantly reduced promoter activity in HepG2 cells, whereas this element in isolation conferred HNF3beta responsiveness to a heterologous promoter. Electrophoretic mobility shift assays were performed to confirm transcription factor:DNA binding. We conclude that HNF3beta and GATA-4 contribute to liver-enriched expression of Hex. |
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Authors:
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L A Denson; M H McClure; C W Bogue; S J Karpen; H C Jacobs |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Gene Volume: 246 ISSN: 0378-1119 ISO Abbreviation: Gene Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-31 Completed Date: 2000-05-31 Revised Date: 2010-08-09 |
Medline Journal Info:
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Nlm Unique ID: 7706761 Medline TA: Gene Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 311-20 Citation Subset: IM |
Affiliation:
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The Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. lee.denson@yale.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AF132550 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals COS Cells Cell Line DNA / chemistry, genetics, metabolism DNA-Binding Proteins / genetics, metabolism, physiology* GATA4 Transcription Factor Genes, Homeobox / genetics Hepatocyte Nuclear Factor 3-beta Homeodomain Proteins / genetics* Humans Liver / cytology, metabolism* Luciferases / genetics, metabolism Male Mice Molecular Sequence Data Nuclear Proteins / genetics, metabolism, physiology* Plasmids Promoter Regions, Genetic / genetics Protein Binding Rats Rats, Sprague-Dawley Recombinant Fusion Proteins / genetics, metabolism Sequence Analysis, DNA Sp1 Transcription Factor / genetics, metabolism, physiology Sp3 Transcription Factor Transcription Factors / genetics, metabolism, physiology* Transcriptional Activation Transfection Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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DK-02318/DK/NIDDK NIH HHS; HD-07388/HD/NICHD NIH HHS; R01 DK056239-02/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/FOXA2 protein, human; 0/Foxa2 protein, mouse; 0/Foxa2 protein, rat; 0/GATA4 Transcription Factor; 0/HHEX protein, human; 0/Hhex protein, mouse; 0/Hhex protein, rat; 0/Homeodomain Proteins; 0/Nuclear Proteins; 0/Recombinant Fusion Proteins; 0/Sp1 Transcription Factor; 0/Transcription Factors; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; 148710-94-5/Sp3 Transcription Factor; 9007-49-2/DNA; EC 1.13.12.-/Luciferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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