title: Identification of novel pancreas-specific regulatory sequences in the promoter region of human pancreatic secretory trypsin inhibitor gene.
abstract: 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.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmachi
authors.forename: M
authors.initials: M
authors.lastname: Katsuki
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
authors.forename: A
authors.initials: A
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Monden
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D011993:Recombinant Fusion Proteins; D014359:Trypsin Inhibitor, Kazal Pancreatic; D015500:Chloramphenicol O-Acetyltransferase