Identification of novel pancreas-specific regulatory sequences in the promoter region of human pancreatic secretory trypsin inhibitor gene.

The human pancreatic secretory trypsin inhibitor (PSTI) genes introduced into mice are specifically expressed in pancreas. The 1.0 kilobase pairs of PSTI 5'-flanking sequence directed preferential expression of a linked reporter chloramphenicol acetyltransferase, which was active in a PSTI-expressing pancreatic cell line (AR42j) but not in a PSTI-nonexpressing fibroblast cell line (XC). Two positively acting elements were found, Region I (-161/-116) and Region II (-103/-74), as defined by transfection and binding assays with AR42j cells. Region II is sufficient for the pancreas-specific expression, but the presence of both Regions I and II is needed for the maximum activity. Sequence studies also revealed that these two elements differ from the previously identified recognition sequence for pancreas transcription factor 1 (PTF1). When the same set of experiments was done with XC cells, one negatively acting element was identified, Region IV (-154/-137). Interestingly, Regions I and IV share a core sequence (-149/-139), CAATCAATAAC. These results suggest that this novel element regulates the human PSTI gene expression positively in pancreatic cells but negatively in nonpancreatic cells.