Single-cell stochastic gene expression kinetics with coupled positive-plus-negative feedback
| Autor: | Jia, Chen, Wang, Le Yi, Yin, George G., Zhang, Michael Q. |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Phys. Rev. E 100, 052406 (2019) |
| Druh dokumentu: | Working Paper |
| DOI: | 10.1103/PhysRevE.100.052406 |
| Popis: | Here we investigate single-cell stochastic gene expression kinetics in a minimal coupled gene circuit with positive-plus-negative feedback. A triphasic stochastic bifurcation upon the increasing ratio of the positive and negative feedback strengths is observed, which reveals a strong synergistic interaction between positive and negative feedback loops. We discover that coupled positive-plus-negative feedback amplifies gene expression mean but reduces gene expression noise over a wide range of feedback strengths when promoter switching is relatively slow, stabilizing gene expression around a relatively high level. In addition, we study two types of macroscopic limits of the discrete chemical master equation model: the Kurtz limit applies to proteins with large burst frequencies and the L\'{e}vy limit applies to proteins with large burst sizes. We derive the analytic steady-state distributions of the protein abundance in a coupled gene circuit for both the discrete model and its two macroscopic limits, generalizing the results obtained in [Chaos 26:043108, 2016]. We also obtain the analytic time-dependent protein distribution for the classical Friedman-Cai-Xie random bursting model proposed in [Phys. Rev. Lett. 97:168302, 2006]. Our analytic results are further applied to study the structure of gene expression noise in a coupled gene circuit and a complete decomposition of noise in terms of five different biophysical origins is provided. Comment: 27 pages, 7 figures |
| Databáze: | arXiv |
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