(Right panels) Mode of action of the DOX-controllable transrepressor. (A) In the absence of DOX, tTR-KRAB binds to tetO and suppresses H1-mediated siRNA transcription, thus allowing normal expression of the cellular target gene (on). (B) In the presence of DOX, tTR-KRAB cannot bind to tetO and hence siRNAs are produced, leading to downregulation of their target (off). The internal marker contained in the siRNA vectors provides an inverse monitoring device, as it is on in the presence of DOX and off in its absence.