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Scientific article
English

The zinc finger-containing transcription factor Gata-4 is expressed in the developing endocrine pancreas and activates glucagon gene expression

Published inMolecular endocrinology, vol. 19, no. 3, p. 759-770
Publication date2005
Abstract

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.

Keywords
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Differentiation
  • Cell Line
  • Cell Nucleus/metabolism
  • Chloramphenicol O-Acetyltransferase/metabolism
  • Cricetinae
  • DNA-Binding Proteins/chemistry/metabolism
  • Dose-Response Relationship, Drug
  • GATA4 Transcription Factor
  • GATA6 Transcription Factor
  • Gene Expression Regulation
  • Glucagon/metabolism
  • Humans
  • Islets of Langerhans/metabolism
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Mutation
  • Pancreas/embryology
  • Promoter Regions, Genetic
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tissue Distribution
  • Transcription Factors/chemistry/metabolism
  • Transcriptional Activation
  • Transfection
  • Zinc Fingers
Citation (ISO format)
RITZ-LASER, Beate et al. The zinc finger-containing transcription factor Gata-4 is expressed in the developing endocrine pancreas and activates glucagon gene expression. In: Molecular endocrinology, 2005, vol. 19, n° 3, p. 759–770. doi: 10.1210/me.2004-0051
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Article (Published version)
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Identifiers
ISSN of the journal0888-8809
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