The study by Manfred Gosse and Hermann Bujard describes the development of a highly efficient regulatory system in mammalian cells using tetracycline-responsive promoters. By fusing the tetracycline repressor (tetR) with the activating domain of herpes simplex virus (HSV) virion protein 16, they created a tetracycline-controlled transactivator (tTA) that is constitutively expressed in HeLa cells. This tTA stimulates transcription from a minimal promoter sequence derived from the human cytomegalovirus promoter IE combined with tetracycline operator (tetO) sequences. When a luciferase gene controlled by a tTA-dependent promoter is integrated into a tTA-producing HeLa cell line, the luciferase activity can be regulated over five orders of magnitude by varying the concentration of tetracycline in the culture medium. This system allows for precise control of gene expression and can be used to create "on/off" situations for genes in a reversible manner. The authors highlight the advantages of this system over other regulatory systems, such as the lac repressor/operator/inducer system, including its rapid and efficient induction, lack of leakiness, and the ability to maintain low tTA concentrations to avoid squelching effects. The system has potential applications in studying gene function and analyzing mRNA decay rates under physiological conditions.The study by Manfred Gosse and Hermann Bujard describes the development of a highly efficient regulatory system in mammalian cells using tetracycline-responsive promoters. By fusing the tetracycline repressor (tetR) with the activating domain of herpes simplex virus (HSV) virion protein 16, they created a tetracycline-controlled transactivator (tTA) that is constitutively expressed in HeLa cells. This tTA stimulates transcription from a minimal promoter sequence derived from the human cytomegalovirus promoter IE combined with tetracycline operator (tetO) sequences. When a luciferase gene controlled by a tTA-dependent promoter is integrated into a tTA-producing HeLa cell line, the luciferase activity can be regulated over five orders of magnitude by varying the concentration of tetracycline in the culture medium. This system allows for precise control of gene expression and can be used to create "on/off" situations for genes in a reversible manner. The authors highlight the advantages of this system over other regulatory systems, such as the lac repressor/operator/inducer system, including its rapid and efficient induction, lack of leakiness, and the ability to maintain low tTA concentrations to avoid squelching effects. The system has potential applications in studying gene function and analyzing mRNA decay rates under physiological conditions.