BackgroundPresent technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression.Methodology/Principal FindingsHere, we show that a chromosomally integrated yeast ‘Leu3p-α-ΙΡΜ’ system constitutes a ligand-inducible regulatory “off-on” genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of α-isopropylmalate (α-ΙΡΜ) in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable α-IPM presents an EC50 equal to 0.8837 mM and fast “OFF-ON” kinetics (t50ON = 43 min, t50OFF = 2.18 h), it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo.Conclusions/SignificanceOur results demonstrate that the ‘Leu3p-α-ΙΡΜ’ constitutes a simpler and safer system for inducible gene expression in biomedical applications.
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