{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:47:15Z","timestamp":1791308835506,"version":"4.3.1"},"reference-count":52,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucagon gene expression in the endocrine pancreas is controlled by three islet-specific elements (G3, G2, and G4) and the\u03b1 -cell-specific element G1. Two proteins interacting with G1 have previously been identified as Pax6 and Cdx2\/3. We identify here the third yet uncharacterized complex on G1 as hepatocyte nuclear factor 3 (HNF-3)\u03b2, a member of the HNF-3\/forkhead transcription family, which plays an important role in the development of endoderm-related organs. HNF-3 has been previously demonstrated to interact with the G2 element and to be crucial for glucagon gene expression; we thus define a second binding site for this transcription on the glucagon gene promoter. We demonstrate that both HNF-3\u03b1 and -\u03b2 produced in heterologous cells can interact with similar affinities to either the G1 or G2 element. Pax6, which binds to an overlapping site on G1, exhibited a greater affinity as compared with HNF-3\u03b1 or -\u03b2. We show that both HNF-3\u03b2 and -\u03b1 can transactivate glucagon gene transcription through the G2 and G1 elements. However, HNF-3 via its transactivating domains specifically impaired Pax6-mediated transactivation of the glucagon promoter but had no effect on transactivation by Cdx2\/3. We suggest that HNF-3 may play a dual role on glucagon gene transcription by 1) inhibiting the transactivation potential of Pax6 on the G1 and G3 elements and 2) direct activation through G1 and G2.<\/jats:p>","DOI":"10.1210\/mend.16.1.0752","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:31:13Z","timestamp":1389202273000},"page":"170-183","source":"Crossref","is-referenced-by-count":42,"title":["Hepatic Nuclear Factor-3 (HNF-3 or Foxa2) Regulates Glucagon Gene Transcription by Binding to the G1 and G2 Promoter Elements"],"prefix":"10.1210","volume":"16","author":[{"given":"Benoit R.","family":"Gauthier","sequence":"first","affiliation":[{"name":"Unite\u0301 de Diabe\u0301tologie Clinique, Centre Me\u0301dical Universitaire, 1211 Gene\u0300ve 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie M.","family":"Schwitzgebel","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Diabe\u0301tologie Clinique, Centre Me\u0301dical Universitaire, 1211 Gene\u0300ve 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia","family":"Zaiko","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Diabe\u0301tologie Clinique, Centre Me\u0301dical Universitaire, 1211 Gene\u0300ve 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Mamin","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Diabe\u0301tologie Clinique, Centre Me\u0301dical Universitaire, 1211 Gene\u0300ve 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Ritz-Laser","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Diabe\u0301tologie Clinique, Centre Me\u0301dical Universitaire, 1211 Gene\u0300ve 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Philippe","sequence":"additional","affiliation":[{"name":"Unite\u0301 de 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