A single element of the elastase I enhancer is sufficient to direct transcription selectively to the pancreas and gut

Mol Cell Biol. 1994 Mar;14(3):2048-57. doi: 10.1128/mcb.14.3.2048-2057.1994.

Abstract

The elastase I (EI) gene is expressed at high levels in the exocrine pancreas and at lower levels in other regions of the gut. The transcriptional enhancer of the EI gene, from nucleotides -205 to -72, recapitulates the expression of the endogenous gene in transgenic mice; it directs not only pancreatic acinar cell expression of a human growth hormone (hGH) transgene but also expression to the stomach, duodenum, and colon. This pattern of selective expression limited to the gastroenteropancreatic organ system is specified by the A element, one of three functional elements in the EI enhancer. When multimerized, the A element directed expression of a hGH reporter gene selectively to the pancreas, stomach, and intestine in transgenic mice. Immunofluorescent localization of hGH indicated that the A element multimer transgenes were expressed in the acinar cells of the pancreas as well as in Brunner's gland cells of the duodenum. The A element binds a pancreatic acinar cell-specific factor, PTF1. Our results show that while the A element is responsible for directing tissue and cell type specificity, other elements of the enhancer must be involved in the regulation of the level of gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Enzymologic*
  • Intestines / enzymology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Pancreas / enzymology*
  • Pancreatic Elastase / genetics*
  • RNA, Messenger / genetics
  • Tissue Distribution
  • Transcription Factors / metabolism

Substances

  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Transcription Factors
  • transcription factor PTF1
  • Pancreatic Elastase