Pdx1 and USF transcription factors co-ordinately regulate Alx3 gene expression in pancreatic ß-cells.
Biochem J
; 463(2): 287-96, 2014 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-25040025
ABSTRACT
Alterations in transcription factors expressed in insulin-producing islet ß-cells generate pancreatic dysfunction leading to diabetes. The homeodomain transcription factor Alx3 (aristaless-like homeobox 3) expressed in pancreatic islets participates in the regulated expression of several islet genes, and its deficiency in mice leads to islet cell apoptosis and glucose intolerance. In the present study, we investigated the mechanisms that regulate expression of Alx3 in pancreatic islets at the transcriptional level. We found that the Alx3 promoter contains at least eight putative regulatory elements with an E-box consensus sequence, three of which were determined to be functional and required for Alx3 promoter activity by mutational analysis in transfected MIN6 ß-cells. We determined that these E-box elements are recognized by the basic helix-loop-helix transcription factors USF1 (upstream stimulatory factor 1) and USF2. We also identified a highly conserved A-box in the Alx3 promoter that is recognized by the islet-specific transcription factor Pdx1 (pancreatic and duodenal homeobox 1). Pdx1-mediated transactivation of the Alx3 promoter requires the integrity of the three functional E-boxes and the co-operation with USF transcription factors bound to them. The results from the present study indicate that Pdx1 contributes to the transcriptional transactivation of Alx3 in pancreatic ß-cells by acting in co-ordination with USF1 and USF2.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transactivadores
/
Regulación de la Expresión Génica
/
Islotes Pancreáticos
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Proteínas de Homeodominio
/
Factores Estimuladores hacia 5'
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem J
Año:
2014
Tipo del documento:
Article