A novel silencer element repressing expression of the GLP-1 receptor gene in fibroblasts and pancreatic A-cells, but not in pancreatic B- and D-cells.

The effects of the incretin hormone glucagon-like peptide 1 (7-36)amide (GLP-1) are mediated by the GLP-1 receptor (GLP-1R). This is expressed in a cell- and tissue-specific manner. Recently, we have cloned the 5'-flanking region of the human GLP-1R gene. The basal promoter activity is driven by the ubiquitous transcription factor Sp1. The tissue- and cell-specific expression of the gene requires several negatively acting cis-regulatory elements. We have now characterized one so far unknown distal cell-specific silencer element (DCS), repressing gene transcription of the human GLP-1R gene in fibroblasts and pancreatic A-cells, but not in pancreatic B- and D-cells. Our data suggests that the basal activity of the GLP-1R promoter is repressed in a tissue- and cell-specific manner by this novel silencer element.