Functional determinants for the tetracycline-dependent transactivator tTA in transgenic mouse embryos

Tetracycline-dependent transgenes promise to be an important tool for investigating the time dependence of gene function during mouse development. The pivotal element of this approach is the recombinant tetracycline-dependent transactivator tTA. Using a modified gene trap approach we successfully generated mouse lines expressing tTA in a wide spread manner during embryogenesis. The transgenic model system which we established allowed us to depict transactivator and target gene expression patterns with high resolution by histochemical means. Our data provide evidence that with decreasing concentrations of tTA protein the state of chromatin acetylation becomes an increasingly important determinant for tTA function. The observation of tTA-dependent position effects on tetO-linked target genes suggests that transcription patterns can be encoded at the level of promoter preactivation.