Expression Variability from a Tet-inducible Positive Feedback Network in Mammalian Cells

From Q-bio

The stochastic nature of gene expression can result in significant cell-to-cell variability in protein levels. Here, we examine gene expression variability from a synthetic gene network in a mammalian system. We have constructed a synthetic mammalian positive feedback circuit in which a tetracycline-regulated transactivator (rtTA) induces its own synthesis in the presence of tetracycline. We analyze interclonal and intraclonal variability in gene expression from several clonal cell lines transduced with the positive feedback network. Finally, we develop a stochastic model of the engineered circuit to investigate the origin of variability in expression from the engineered mammalian gene network. generate predictions that can be tested with further quantitative experimentation.