The POU domain transcription factor Tst-1 activates somatostatin receptor 1 gene expression in pancreatic beta -cells.

The peptide hormone somatostatin inhibits the release of insulin. The gene encoding somatostatin receptor 1 is expressed in pancreatic beta-cells and insulinoma RIN 1046-38 cells. In the present study the mechanisms underlying the regulation of the somatostatin receptor 1 gene in pancreatic beta-cells were investigated. Transient transfections of RIN 1046-38 cells with promoter/reporter gene constructs and footprint analysis revealed two regions, fp1 and fp2, that were necessary for the observed promoter activity. Mutagenesis of the fp2 region delineated the cis-acting element to the motif 5'-TTAATCATT-3'. The POU domain transcription factor Tst-1 was identified as trans-activator mediating the 5'-TTAATCATT-3' motif-dependent transcription in RIN 1046-38 cells and heterologous CV1 cells. Tst-1, known as a transcriptional regulator in keratinocytes, glial cells, and neurons, has been detected by immunohistochemistry in pancreatic islets. Altogether, we demonstrate Tst-1 as transcriptional regulator in pancreatic neuroendocrine cells.