Tetracycline-controlled transcriptional activation

[1] Tetracycline-controlled gene expression is based upon the mechanism of resistance to tetracycline antibiotic treatment found in gram-negative bacteria.

In nature, the Ptet promoter expresses TetR (the repressor) and TetA, the protein that pumps tetracycline antibiotic out of the cell.

[3] The Tet-Off system for controlling expression of genes of interest in mammalian cells was developed by Professors Hermann Bujard [de] and Manfred Gossen at the University of Heidelberg and first published in 1992.

In addition, its expression is considered to be more stable in eukaryotic cells due to being human codon optimized and utilizing three minimal transcriptional activation domains.

It was discovered in 2000 as one of two improved mutants by H. Bujard and his colleagues after random mutagenesis of the Tet repressor part of the transactivator gene.

Expression of the gene of interest is repressed by the high affinity binding of TetR homodimers to each TetO2 sequences in the absence of tetracycline.

A modified version of T-REx is the Linearizer synthetic biological circuit, optimized for gene expression tuning in eukaryotic (budding yeast, human, etc) cells.

Also, since the 19bp tet-o sequence is naturally absent from mammalian cells, pleiotropy is thought to be minimized compared to hormonal methods of control.