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抑制剂改变调控蛋白的随机性,迫使细胞在双稳态系统中切换到另一种状态。

Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System.

机构信息

Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan.

出版信息

Sci Rep. 2017 Jun 30;7(1):4413. doi: 10.1038/s41598-017-04596-7.

DOI:10.1038/s41598-017-04596-7
PMID:28667253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5493615/
Abstract

The cellular behaviors under the control of genetic circuits are subject to stochastic fluctuations, or noise. The stochasticity in gene regulation, far from a nuisance, has been gradually appreciated for its unusual function in cellular activities. In this work, with Chemical Master Equation (CME), we discovered that the addition of inhibitors altered the stochasticity of regulatory proteins. For a bistable system of a mutually inhibitory network, such a change of noise led to the migration of cells in the bimodal distribution. We proposed that the consumption of regulatory protein caused by the addition of inhibitor is not the only reason for pushing cells to the specific state; the change of the intracellular stochasticity is also the main cause for the redistribution. For the level of the inhibitor capable of driving 99% of cells, if there is no consumption of regulatory protein, 88% of cells were guided to the specific state. It implied that cells were pushed, by the inhibitor, to the specific state due to the change of stochasticity.

摘要

在遗传电路的控制下,细胞的行为受到随机波动或噪声的影响。基因调控中的随机性远非一种干扰,它在细胞活动中的独特功能逐渐受到重视。在这项工作中,我们使用化学主方程(CME)发现,抑制剂的添加改变了调控蛋白的随机性。对于一个相互抑制网络的双稳态系统,这种噪声的变化导致细胞在双峰分布中迁移。我们提出,抑制剂的添加导致的调控蛋白消耗并不是将细胞推向特定状态的唯一原因;细胞内随机性的变化也是细胞重新分布的主要原因。对于能够驱动 99%细胞的抑制剂水平,如果没有调控蛋白的消耗,88%的细胞会被引导到特定的状态。这意味着细胞由于随机性的变化而被抑制剂推向特定的状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/64386fdff6be/41598_2017_4596_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/157bc01040a6/41598_2017_4596_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/5b87fc4b1b33/41598_2017_4596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/1721f5e848df/41598_2017_4596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/941fd59836ec/41598_2017_4596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/51c59f5b9a32/41598_2017_4596_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/64386fdff6be/41598_2017_4596_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/157bc01040a6/41598_2017_4596_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/5b87fc4b1b33/41598_2017_4596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/1721f5e848df/41598_2017_4596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/941fd59836ec/41598_2017_4596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/51c59f5b9a32/41598_2017_4596_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8f2/5493615/64386fdff6be/41598_2017_4596_Fig6_HTML.jpg

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