| First Author | Philippe J | Year | 1995 |
| Journal | Mol Endocrinol | Volume | 9 |
| Issue | 3 | Pages | 368-74 |
| PubMed ID | 7776982 | Mgi Jnum | J:23801 |
| Mgi Id | MGI:71490 | Doi | 10.1210/mend.9.3.7776982 |
| Citation | Philippe J (1995) Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene. Mol Endocrinol 9(3):368-74 |
| abstractText | 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. |
