TetO

TetO refers to the tetracycline operator, a DNA regulatory sequence that binds the TetR family repressor. It is part of the bacterial tetracycline resistance system, most commonly described in Escherichia coli as it controls the expression of the tetA efflux pump. TetO functions as a cis-regulatory element upstream of resistance genes, allowing the cell to modulate transcription in response to antibiotic exposure.

In the absence of tetracycline, TetR binds to tetO and represses transcription by blocking RNA polymerase access to the operon. When tetracycline or its analog doxycycline is present, it binds TetR, inducing a conformational change that reduces TetR’s affinity for tetO. TetR dissociates from the operator, enabling transcription of tetA and activation of the resistance mechanism. The system thus links gene expression to the presence of the antibiotic.

Beyond bacterial resistance, tetO sequences have been adapted as versatile tools in genetic engineering. The Tet-On and Tet-Off systems use tetO to control transcription in response to doxycycline in mammalian and other eukaryotic cells. In Tet-On, a reverse Tet transactivator binds tetO and activates transcription only in the presence of doxycycline. In Tet-Off, the original Tet transactivator binds tetO to drive expression in the absence of doxycycline, with expression suppressed when doxycycline is present. These systems typically employ multiple tetO copies near a minimal promoter to achieve tunable expression of a gene of interest.

History and references place tetO within the broader study of bacterial gene regulation and its successful repurposing for inducible gene expression in research and biotechnology. See also TetR and tetracycline resistance.