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Title

Hepatic nuclear factor-3 (HNF-3 or Foxa2) regulates glucagon gene transcription by binding to the G1 and G2 promoter elements
Authors
Gauthier, Benoît
Schwitzgebel Luscher, Valérie
Zaiko, Maia
Mamin, Aline
Ritz, Beate Andréa
Philippe, Jacques
Published in Molecular Endocrinology. 2002, vol. 16, no. 1, p. 170-83
Abstract Glucagon gene expression in the endocrine pancreas is controlled by three islet-specific elements (G3, G2, and G4) and the alpha-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)beta, 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-3alpha and -beta 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-3alpha or -beta. We show that both HNF-3beta and -alpha 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.
Keywords Animals — Base Sequence — Binding Sites — Cell Line — Cricetinae — DNA-Binding Proteins/genetics/metabolism — Eye Proteins — Gene Expression Regulation — Glucagon/genetics/metabolism — Hepatocyte Nuclear Factor 3-alpha — Hepatocyte Nuclear Factor 3-beta — Homeodomain Proteins/genetics/metabolism — Kidney/cytology — Mesocricetus — Molecular Sequence Data — Nuclear Proteins/genetics/metabolism — Paired Box Transcription Factors — Promoter Regions, Genetic — Repressor Proteins — Trans-Activators — Transcription Factors — Transcription, Genetic
Identifiers
PMID: 11773447
Full text
Article (Published version) (575 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Faculté de médecine / Section de médecine clinique / Département de pédiatrie
Research group Etude des altérations du gène ATM dans divers cancers de l'enfant (178)
Citation
(ISO format) 		GAUTHIER, Benoît et al. Hepatic nuclear factor-3 (HNF-3 or Foxa2) regulates glucagon gene transcription by binding to the G1 and G2 promoter elements. In: Molecular Endocrinology, 2002, vol. 16, n° 1, p. 170-83. https://archive-ouverte.unige.ch/unige:55980

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Deposited on : 2015-04-30

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