REPRESSION OF SOMATOSTATIN GENE-TRANSCRIPTION MEDIATED BY 2 PROMOTER SILENCER ELEMENTS

We report that expression of the somatostatin gene in pancreatic islet and in non-islet cells is negatively regulated by two proximal silenc er elements, PS1 and PS2. Transient transfection assays showed that PS 1 decreases somatostatin gene promoter activity stimulated by an upstr eam enhancer in the islet D-cell line RIN-1027-B2, but not in the isle t 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 indepen dently inhibit somatostatin gene promoter activity, suggesting that bo th elements are involved in preventing the expression of the somatosta tin gene in non-islet cells. DNA-binding studies revealed that both PS 1 and PS2 bind similar nuclear protein complexes in islet and non-isle t cells (120 and 130 kDa). PS1 also binds a 100-kDa protein present in islet Band D-cell lines. In addition, both PS1 and PS2 bind three D-c ell-specific proteins (40, 43 and 45 kDa). These observations support a direct involvement of both positive and negative transcriptional con trol mechanisms in the regulation of the islet cell-specific expressio n of the somatostatin gene.