Structure and expression of the chicken proglucagon gene.

The rat and human proglucagon gene immediate promoter regions have differing transcriptional activities in islet cell lines. It is unclear upon which lineage the expression changes have occurred, or which base changes and transcription factors explain the changes in promoter activity. We have studied the expression of the chicken proglucagon gene to better understand changes in mammalian proglucagon gene promoter activity. The chicken proglucagon gene is composed of seven exons, and contains an additional exon that contains much of intervening peptide 1 that has not been seen in any other proglucagon gene. Despite very limited sequence identity between chicken and rat proglucagon promoters, the chicken proglucagon promoter supports reporter gene expression in rodent glucagon-expressing cell lines. These results suggest that the immediate proglucagon promoter region likely has retained ability to be expressed in islet cells, but a few changes to this sequence on the human lineage have extinguished expression of the immediate promoter region. Our work also demonstrate that in contrast to the conserved human proglucagon promoter region which has lost promoter activity that significant changes in proglucagon promoter sequence can occur yet retain expression potential.