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PubMed · 7776982

Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene.

J Philippe
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Abstract

Hepatocyte-nuclear factor 3 beta (HNF-3 beta), a member of the HNF-3 gene family, is expressed in glucagon-producing islet cells and represses glucagon gene expression. We show here that at least three different HNF-3 beta transcripts that encode HNF-3 beta protein variants are present in glucagon-producing cells, HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3. Compared with the HNF-3 beta 1 cDNA, HNF-3 beta 2 cDNA lacks sequences of exon 1 while exons 1 and 4 are absent from the HNF-3 beta 3 cDNA. The deduced amino-acid (aa) sequence of HNF-3 beta 2 and HNF-3 beta 3 proteins differs from HNF-3 beta 1 by a 6-aa amino-terminal extension and by the absence of the first 30 aa, respectively. HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3 bind to the major enhancer of the rat glucagon gene G2 with similar affinity. By contrast to HNF-3 beta 1, which represses glucagon gene expression when overexpressed in the glucagon-producing cell line InR1G9, HNF-3 beta 2 and HNF-3 beta 3 do not affect transcriptional activity. Furthermore, cotransfection of HNF-3 beta 2 or HNF-3 beta 3 along with HNF-3 beta 1 decreases the negative effects of HNF-3 beta 1. We conclude that glucagon gene expression may be regulated by the relative abundance of the three different HNF-3 beta variants in alpha-cells.

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Amino Acid SequenceAnimalsBase SequenceCell LineCloning, MolecularCricetinaeDNA ProbesDNA, ComplementaryDNA-Binding ProteinsExonsGlucagonHepatocyte Nuclear Factor 3-betaMiceMolecular Sequence DataNuclear ProteinsNucleic Acid HybridizationOpen Reading FramesPolymerase Chain ReactionRNA, MessengerRatsStructure-Activity RelationshipTranscription FactorsTranscription, GeneticTranscriptional ActivationTransfectionJournal ArticleResearch Support, Non-U.S. Gov't

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J Philippe. 1995. Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene.. https://doi.org/10.1210/mend.9.3.7776982

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