A novel RU486 inducible system for the activation and repression of genes.

We have developed an inducible system that consists of a transactivator and a target gene. The transactivator encodes a chimeric regulator that is responsive to RU486 (mifepristone, a progesterone receptor antagonist) 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 induces target gene expression by binding to the Gal4 recognition sequences upstream of the target. To verify this concept, we have successfully demonstrated the functionality of this system in tissue culture and in transgenic mice. Furthermore, for applications that require higher levels of a target gene, we also have generated regulators that can induce greater target gene expression. In addition, we also have constructed a modified regulator which can repress gene expression. The versatility of our system should prove useful for many applications in biology and gene therapy.