Tetracycline regulated transcriptional modulators with altered DNA binding specificities
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United States of America Patent
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Dec 31, 1996
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N/A
app pub date -
Jun 7, 1995
filing date -
Jun 14, 1993
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Abstract
Isolated nucleic acid molecules encoding fusion proteins which regulate transcription in eukaryotic cells are disclosed. The fusion proteins of the invention comprise a Tet repressor having at least one amino acid mutation that confers on the fusion protein an ability to bind a class B tet operator sequence having a nucleotide substitution at position +4 or +6, operatively linked to a polypeptide which regulates transcription in eukaryotic cells. Methods for regulating transcription of a tet operator-linked gene in a cell are also provided. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a fusion protein which regulates transcription, the fusion protein comprising a Tet repressor having at least one amino acid mutation that confers on the fusion protein an ability to bind a class B tet operator sequence having a nucleotide substitution at position +4 or +6, operatively linked to a polypeptide which regulates transcription in eukaryotic cells, and modulating the concentration of a tetracycline, or analogue thereof, in contact with the cell.
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