Regulation by competition: a hidden layer of gene regulatory network

Background Molecular competition brings about trade‐offs of shared limited resources among the cellular components, and thus introduces a hidden layer of regulatory mechanism by connecting components even without direct physical interactions. Several molecular competition scenarios have been observed recently, but there is still a lack of systematic quantitative understanding to reveal the essence of molecular competition. Methods Here, by abstracting the analogous competition mechanism behind diverse molecular systems, we built a unified coarse‐grained competition motif model to systematically integrate experimental evidences in these processes and analyzed general properties shared behind them from steady‐state behavior to dynamic responses. Results We could predict in what molecular environments competition would reveal threshold behavior or display a negative linear dependence. We quantified how competition can shape regulator‐target dose‐response curve, modulate dynamic response speed, control target expression noise, and introduce correlated fluctuations between targets. Conclusions This work uncovered the complexity and generality of molecular competition effect as a hidden layer of gene regulatory network, and therefore provided a unified insight and a theoretical framework to understand and employ competition in both natural and synthetic systems.