Pdx1 and USF transcription factors coordinately regulate Alx3 gene expression in pancreatic {beta} cells

In this 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 b cells. We determined that these E-box elements are recognized by the basic helix–loop–helix transcription factors USF (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. Pdx1-mediated transactivation of the Alx3 promoter requires the integrity of the three functional E-boxes and the cooperation with USF transcription factors bound to them. Our results indicate that Pdx1 contributes to the transcriptional transactivation of Alx3 in pancreatic b cells by acting in coordination with USF1 and USF2.
Source: BJ Gene - Category: Biochemistry Authors: Tags: BJ Gene Source Type: research