文献类型：期刊文献

英文题名：Noise Propagation in Gene Regulation Networks Involving Interlinked Positive and Negative Feedback Loops

作者：Zhang, Hui[1];Chen, Yueling[1,2];Chen, Yong[1,3]

第一作者：Zhang, Hui

通信作者：Chen, Y[1]

机构：[1]Lanzhou Univ, Inst Theoret Phys, Lanzhou 730000, Peoples R China;[2]Gansu Coll Tradit Chinese Med, Dept Phys, Lanzhou, Peoples R China;[3]Kings Coll London, Dept Math, London WC2R 2LS, England

第一机构：Lanzhou Univ, Inst Theoret Phys, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Inst Theoret Phys, Lanzhou 730000, Peoples R China.

年份：2012

卷号：7

期号：12

外文期刊名：PLOS ONE

收录：;Scopus(收录号：2-s2.0-84871424881);WOS:【SCI-EXPANDED(收录号:WOS:000312794500053)】；

基金：This work was supported by the National Natural Science Foundation of China (Grants No. 10975063), the Fundamental Research Funds for the Central Universities (Grant No. lzujbky-2012-17), and the Program for New Century Excellent Talents in University (Grant No. NCET-11-0206). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

摘要：It is well known that noise is inevitable in gene regulatory networks due to the low-copy numbers of molecules and local environmental fluctuations. The prediction of noise effects is a key issue in ensuring reliable transmission of information. Interlinked positive and negative feedback loops are essential signal transduction motifs in biological networks. Positive feedback loops are generally believed to induce a switch-like behavior, whereas negative feedback loops are thought to suppress noise effects. Here, by using the signal sensitivity (susceptibility) and noise amplification to quantify noise propagation, we analyze an abstract model of the Myc/E2F/MiR-17-92 network that is composed of a coupling between the E2F/Myc positive feedback loop and the E2F/Myc/miR-17-92 negative feedback loop. The role of the feedback loop on noise effects is found to depend on the dynamic properties of the system. When the system is in monostability or bistability with high protein concentrations, noise is consistently suppressed. However, the negative feedback loop reduces this suppression ability (or improves the noise propagation) and enhances signal sensitivity. In the case of excitability, bistability, or monostability, noise is enhanced at low protein concentrations. The negative feedback loop reduces this noise enhancement as well as the signal sensitivity. In all cases, the positive feedback loop acts contrary to the negative feedback loop. We also found that increasing the time scale of the protein module or decreasing the noise autocorrelation time can enhance noise suppression; however, the systems sensitivity remains unchanged. Taken together, our results suggest that the negative/positive feedback mechanisms in coupled feedback loop dynamically buffer noise effects rather than only suppressing or amplifying the noise.