A SINGLE-ELEMENT OF THE ELASTASE-I ENHANCER IS SUFFICIENT TO DIRECT TRANSCRIPTION SELECTIVELY TO THE PANCREAS AND GUT

The elastase I (EI) gene is expressed at high levels in the exocrine p ancreas and at lower levels in other regions of the gut. The transcrip tional enhancer of the EI gene, from nucleotides -205 to -72, recapitu lates the expression of the endogenous gene in transgenic mice; it dir ects not only pancreatic acinar cell expression of a human growth horm one (hGH) transgene but also expression to the stomach, duodenum, and colon. This pattern of selective expression limited to the gastroenter opancreatic organ system is specified by the A element, one of three f unctional elements in the EI enhancer. When multimerized, the A elemen t directed expression of a hGH reporter gene selectively to the pancre as, stomach, and intestine in transgenic mice, Immunofluorescent local ization of hGH indicated that the A element multimer transgenes were e xpressed in the acinar cells of the pancreas as well as in Brunner's g land cells of the duodenum. The A element binds a pancreatic acinar ce ll-specific factor, PTF1. Our results show that while the A element is responsible for directing tissue and cell type specificity, other ele ments of the enhancer must be involved in the regulation of the level of gene expression.