Tissue-specific expression of the rat insulin 1 gene in vivo requires both 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 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.
Dandoy-Dron
F
F
Institut Cochin de Génétique Moléculaire, INSERM unité 257, CHU Cochin-Port Royal, Paris, France.
Itier
J M
JM
Monthioux
E
E
Bucchini
D
D
Jami
J
J
D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000235:genetics*; D007340:Insulinoma / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D014407:Tumor Cells, Cultured
D007328:Insulin