A NOVEL RU486 INDUCIBLE SYSTEM FOR THE ACTIVATION AND REPRESSION OF GENES

We have developed an inducible system that consists of a transactivato r and a target gene. The transactivator encodes a chimeric regulator t hat is responsive to RU486 (mifepristone, a progesterone receptor anta gonist) but not to progestins and other hormones or endogenous ligands for activation. The target gene can be any gene under the control of Gal4 DNA binding sites. When the regulator is activated by RU486, it i nduces target gene expression by binding to the Gal4 recognition seque nces upstream of the target. To verify this concept, we have successfu lly demonstrated the functionality of this system in tissue culture an d in transgenic mice. Furthermore, for applications that require highe r levels of a target gene, we also have generated regulators that can induce greater target gene expression. In addition, we also have const ructed a modified regulator which can repress gene expression. The ver satility of our system should prove useful for many applications in bi ology and gene therapy. (C) 1998 Elsevier Science B.V.