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

Autor: Beate Ritz-Laser, Jacques Philippe, Thierry Brun, Aline Mamin, Valerie M. Schwitzgebel, Isabelle Avril
Rok vydání: 2004
Předmět:
Time Factors
Glucagonoma
Mice
Endocrinology
Cricetinae
GATA6 Transcription Factor
Tissue Distribution
Promoter Regions
Genetic
ddc:616
DNA-Binding Proteins/chemistry/metabolism
Zinc finger
ddc:618
Reverse Transcriptase Polymerase Chain Reaction
GATA2
Cell Differentiation
Zinc Fingers
General Medicine
Pancreas/embryology
Cell biology
DNA-Binding Proteins
medicine.anatomical_structure
Transcription Factors/chemistry/metabolism
embryonic structures
Islets of Langerhans/metabolism
Endoderm
Pancreas
Protein Binding
Chloramphenicol O-Acetyltransferase
Transcriptional Activation
endocrine system
medicine.medical_specialty
Molecular Sequence Data
Chloramphenicol O-Acetyltransferase/metabolism
Biology
Transfection
Glucagon
Cell Line
Islets of Langerhans
Internal medicine
medicine
Animals
Humans
Glucagon/metabolism
ddc:612
Molecular Biology
Transcription factor
Gene
Cell Nucleus
Binding Sites
Base Sequence
Dose-Response Relationship
Drug
medicine.disease
GATA4 Transcription Factor
Gene Expression Regulation
Microscopy
Fluorescence
Cell Nucleus/metabolism
Mutation
Transcription Factors
Zdroj: Molecular Endocrinology, Vol. 19, No 3 (2005) pp. 759-70
ISSN: 0888-8809
Popis: 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.
Databáze: OpenAIRE
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