Regulation of Gene Activation by Competitive Cross Talking Pathways

The phenomenon of a gene expression burst has been attributed to random transitions between the active and inactive states of a gene. However, the mechanisms underlying regulation of the activation process in response to environmental changes remain unclear. Here, we model gene activation as a consequence of the competitive cross talk between a weak basal pathway and an inducible signaling pathway and reveal rich expression dynamics along with intricate dependence of noise and Fano factor on mean expression levels. These theoretical results are in good agreement with a large experimental data set in Escherichia coli, yeast, and mammalian cells. Furthermore, both theoretical analyses and supporting biological evidence converge to demonstrate the existence of a tradeoff that governs the sharp up- and downregulation of gene expression, suggesting an ordered scenario that activates a gene under varying conditions. These regulation modes, together with cross talk pathways, may provide new guidance for the analysis and interpretation of genetic data in various applications, ranging from genetic engineering to therapeutic targets of disease.