Repression of somatostatin gene transcription mediated by two promoter silencer elements

Abstract

We report that expression of the somatostatin gene in pancreatic islet and in non-islet cells is negatively regulated by two proximal silencer elements, PS1 and PS2. Transient transfection assays showed that PS1 decreases somatostatin gene promoter activity stimulated by an upstream enhancer in the islet D-cell line RIN-1027-B2, but not in the islet B-cell line RIN-1046-38, whereas PS2 inhibits gene transcription in both B- and D-cell lines. In BHK fibroblasts, both PS1 and PS2 independently inhibit somatostatin gene promoter activity, suggesting that both elements are involved in preventing the expression of the somatostatin gene in non-islet cells. DNA-binding studies revealed that both PS1 and PS2 bind similar nuclear protein complexes in islet and non-islet cells (120 and 130 kDa). PS1 also binds a 100-kDa protein present in islet B- and D-cell lines. In addition, both PS1 and PS2 bind three D-cell-specific protiens (40, 43 and 45 kDa). These observations support a direct involvement of both positive and negative transcriptional control mechanisms in the regulation of the islet cell-specific expression of the somatostatin gene.