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.