Potent genetic switch allowing regulated gene expression in eukaryotic

Abstract

The present invention provides a system for controlled transgene transcription using chimeric activator and repressor proteins functioning in a novel regulatory network. The target transgene is actively silenced in non-inducing conditions by a novel class of chimeric proteins consisting of the DNA-binding tetracycline repressor fused to distinct multimerized eukaryotic transcriptional repression domains. In the presence of a tetracycline 'inducer', the repressor does not bind to the promoters for both the target gene and for another regulatory gene encoding a transactivator (e.g., GAL4-VP16). Under these inducing conditions, the transactivator activates expression of the target transgene and of its own gene, in an additional autoregulatory positive feedback loop.