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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2005-2-24
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pubmed:abstractText |
Gene inactivation studies have shown that members of the Gata family of transcription factors are critical for endoderm development throughout evolution. We show here that Gata-4 and/or Gata-6 are not only expressed in the adult exocrine pancreas but also in glucagonoma and insulinoma cell lines, whereas Gata-5 is restricted to the exocrine pancreas. During pancreas development, Gata-4 is expressed already at embryonic d 10.5 and colocalizes with early glucagon+ cells at embryonic d 12.5. Gata-4 was able to transactivate the glucagon gene both in heterologous BHK-21 (nonislet Syrian baby hamster kidney) and in glucagon-producing InR1G9 cells. Using gel-mobility shift assays, we identified a complex formed with nuclear extracts from InR1G9 cells on the G5 control element (-140 to -169) of the glucagon gene promoter as Gata-4. Mutation of the GATA binding site on G5 abrogated the transcriptional activation mediated by Gata-4 and reduced basal glucagon gene promoter activity in glucagon-producing cells by 55%. Furthermore, Gata-4 acted more than additively with Forkhead box A (hepatic nuclear factor-3) to trans-activate the glucagon gene promoter. We conclude that, besides its role in endoderm differentiation, Gata-4 might be implicated in the regulation of glucagon gene expression in the fetal pancreas and that Gata activity itself may be modulated by interactions with different cofactors.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
759-70
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15539431-Animals,
pubmed-meshheading:15539431-Base Sequence,
pubmed-meshheading:15539431-Binding Sites,
pubmed-meshheading:15539431-Cell Differentiation,
pubmed-meshheading:15539431-Cell Line,
pubmed-meshheading:15539431-Cell Nucleus,
pubmed-meshheading:15539431-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:15539431-Cricetinae,
pubmed-meshheading:15539431-DNA-Binding Proteins,
pubmed-meshheading:15539431-Dose-Response Relationship, Drug,
pubmed-meshheading:15539431-GATA4 Transcription Factor,
pubmed-meshheading:15539431-GATA6 Transcription Factor,
pubmed-meshheading:15539431-Gene Expression Regulation,
pubmed-meshheading:15539431-Glucagon,
pubmed-meshheading:15539431-Humans,
pubmed-meshheading:15539431-Islets of Langerhans,
pubmed-meshheading:15539431-Mice,
pubmed-meshheading:15539431-Microscopy, Fluorescence,
pubmed-meshheading:15539431-Molecular Sequence Data,
pubmed-meshheading:15539431-Mutation,
pubmed-meshheading:15539431-Pancreas,
pubmed-meshheading:15539431-Promoter Regions, Genetic,
pubmed-meshheading:15539431-Protein Binding,
pubmed-meshheading:15539431-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15539431-Time Factors,
pubmed-meshheading:15539431-Tissue Distribution,
pubmed-meshheading:15539431-Transcription Factors,
pubmed-meshheading:15539431-Transcriptional Activation,
pubmed-meshheading:15539431-Transfection,
pubmed-meshheading:15539431-Zinc Fingers
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pubmed:year |
2005
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pubmed:articleTitle |
The zinc finger-containing transcription factor Gata-4 is expressed in the developing endocrine pancreas and activates glucagon gene expression.
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pubmed:affiliation |
Diabetes Unit, University Hospital Geneva, 24, rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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