BETA2 activates transcription from the upstream glucokinase gene promoter in islet beta-cells and gut endocrine cells.
Diabetes
; 52(2): 403-8, 2003 Feb.
Article
en En
| MEDLINE
| ID: mdl-12540614
ABSTRACT
Glucokinase (GK) gene transcription initiates in the islet (beta-cell), gut, and brain from promoter sequences residing approximately 35 kbp upstream from those used in liver. Expression of betaGK is controlled in beta-cells by cell-enriched (i.e. pancreatic duodenal homeobox 1 [PDX-1]) and ubiquitously (i.e., Pal) distributed factors that bind to and activate from conserved sequence motifs within the upstream promoter region (termed betaGK). Here, we show that a conserved E-box element also contributes to control in the islet and gut. betaGK promoter-driven reporter gene activity was diminished by mutating the specific sequences involved in E-box-mediated basic helix-loop-helix factor activator binding in islet beta-cells and enteroendocrine cells. Gel shift assays demonstrated that the betaGK and insulin gene E-box elements formed the same cell-enriched (BETA2E47) and generally distributed (upstream stimulatory factor [USF]) protein-DNA complexes. betaGK E-box-driven activity was stimulated in cotransfection assays performed in baby hamster kidney (BHK) cells with BETA2 and E47, but not USF. Chromatin immunoprecipitation assays performed with BETA2 antisera showed that BETA2 occupies the upstream promoter region of the endogenous betaGK gene in beta-cells. We propose that BETA2 (also termed NeuroD1) regulates betaGK promoter activity.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Transactivadores
/
Regulación de la Expresión Génica
/
Islotes Pancreáticos
/
Regiones Promotoras Genéticas
/
Proteínas de Unión al ADN
/
Glucoquinasa
/
Mucosa Intestinal
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Diabetes
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos