TISSUE-SPECIFIC EXPRESSION OF THE RAT INSULIN-1 GENE IN-VIVO REQUIRESBOTH THE ENHANCER AND PROMOTER REGIONS

The tissue specificity conferred by cis-acting regulatory elements of the rat insulin 1 gene was examined in both cultured cells and transge nic mice. The enhancer region (-346/-103) coupled to a ubiquitous prom oter activated expression of a reporter gene in insulinoma cells but n ot in fibroblasts, in agreement with our previous work, and the specif ic expression was limited to a subregion containing the FAR and FLAT e lements (-252/-199). In transgenic mice, however, this FAR-FLAT minien hancer alone failed to activate a reporter gene. Under the same condit ions, in vivo, the enhancer (-346/-103) activated gene expression, but did not confer complete pancreatic specificity. The transgene, in thi s case, was expressed in pancreas and also in brain. Reassociation of the rat insulin 1 promoter (-102/+9) with the enhancer (-346/-103) pre vented expression in brain and thus restored pancreatic specificity. A ll of these observations indicate that tissue-specific expression of t he rat insulin 1 gene, in vivo, results from interaction of multiple s equence elements and not from any single minimal sequence.