Tissue-specific expression of the rat insulin 1 gene in vivo requires both the enhancer and promoter regions

Differentiation. 1995 Apr;58(4):291-5. doi: 10.1046/j.1432-0436.1995.5840291.x.

Abstract

The tissue specificity conferred by cis-acting regulatory elements of the rat insulin 1 gene was examined in both cultured cells and transgenic mice. The enhancer region (-346/-103) coupled to a ubiquitous promoter activated expression of a reporter gene in insulinoma cells but not in fibroblasts, in agreement with our previous work, and the specific expression was limited to a subregion containing the FAR and FLAT elements (-252/-199). In transgenic mice, however, this FAR-FLAT minienhancer alone failed to activate a reporter gene. Under the same conditions, in vivo, the enhancer (-346/-103) activated gene expression, but did not confer complete pancreatic specificity. The transgene, in this case, was expressed in pancreas and also in brain. Reassociation of the rat insulin 1 promoter (-102/+9) with the enhancer (-346/-103) prevented expression in brain and thus restored pancreatic specificity. All of these observations indicate that tissue-specific expression of the rat insulin 1 gene, in vivo, results from interaction of multiple sequence elements and not from any single minimal sequence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Enhancer Elements, Genetic*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • In Vitro Techniques
  • Insulin / genetics*
  • Insulinoma / genetics
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Organ Specificity
  • Pancreatic Neoplasms / genetics
  • Promoter Regions, Genetic*
  • Rats
  • Tumor Cells, Cultured

Substances

  • Insulin