TISSUE-SPECIFICITY OF A GLUCOCORTICOID-DEPENDENT ENHANCER IN TRANSGENIC MICE

The glucocorticoid-responsive units (GRUs) of the rat tyrosine aminotr ansferase were associated with the regulatory sequences of a cellular gene expressed ubiquitously-that coding for the largest subunit of RNA polymerase II. In transient expression assays,glucocorticoid responsi veness of the hybrid regulatory regions depends on the spatial relatio nship and number of regulatory elements. Two parameters affect the rat io of induction by glucocorticoids: the basal level of the hybrid prom oter that is affected by the RNA polymerase II regulatory sequences an d the glucocorticoid-induced level that depends on the;distance betwee n the GRUs and the TATA box. A fully active glucocorticoid-responsive hybrid gene was used to generate transgenic mice. Results show that a composite regulatory pattern is obtained: ubiquitous basal expression characteristic of the RNA polymerase II gene and liver-specific glucoc orticoid activation characteristic of the tyrosine aminotransferase GR Us, This result demonstrates that the activity of the tyrosine aminotr ansferase GRUs is cell-type-specific not only in cultured cells but al so in the whole animal.