US 5,789,156 · Granted 1998-08-04

Tetracycline-regulated transcriptional inhibitors

Nucleic acid molecules and proteins useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is inhibited by a transcriptional inhibitor fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences either (i) in the absence but not the presence of tetracycline (or an analogue thereof) or (ii) in the presence but not the absence of tetracycline (or an analogue thereof), and a second polypeptide which directly or indirectly inhibits transcription in eukaryotic cells. In one embodiment, the fusion protein comprises a Tet repressor operatively linked to a transcriptional silencer polypeptide. In another embodiment, the fusion protein comprises a mutated Tet repressor operatively linked to a transcriptional silencer polypeptide. The fusion proteins of the invention are useful for reducing the level of transcription of a tet operator-linked target gene. Moreover, the fusion proteins of the invention can be used in combination with tetracycline-regulated transcriptional activator fusion proteins to allow for precise regulation of the expression of one or multiple target genes. Kits including the components of the regulatory system of the invention are also encompassed by the invention.

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