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Regulation by competition: a hidden layer of gene regulatory network
Authors:Lei Wei  Ye Yuan  Tao Hu  Shuailin Li  Tianrun Cheng  Jinzhi Lei  Zhen Xie  Michael Q Zhang  Xiaowo Wang
Abstract: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.
Keywords:systems biology  computational modeling  molecular competition regulation  synthetic biology  network motif  
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