Interlinking positive and negative feedback loops creates a tunable motif in gene regulatory networks
Interlinking positive and negative feedback loops creates a tunable motif in gene regulatory networks
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相互链接的正反馈环和负反馈环在基因调控网络中创建了一个可调节的基序
DOI：
10.1103/physreve.80.011926
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发表时间：
2009-07-01
影响因子：
2.4
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Tian, Xiao-Jun;Zhang, Xiao-Peng;Wang, Wei
在基因调控网络中，正反馈环和负反馈环经常被耦合以执行各种功能，充当开关、振荡器和可兴奋装置。这意味着，这样一个系统与相互联系的积极和消极的反馈回路是一个灵活的母题，可以调节自己的各种功能。在这里，我们开发了一个最小的系统模型，并系统地探讨了它的动态和性能优势，在一个统一的框架中的刺激。当反馈环的强度改变时，系统确实表现出不同的行为。首先，通过增加正反馈的强度，系统可以从单稳态调节到双稳态，而双稳态区域由负反馈的强度调制。第二，随着负反馈强度的增加，系统经历了从双稳态到兴奋性和振荡性的转变，而随着正反馈强度的增加，系统发生了反向的转变。第三，该系统比单个反馈回路更灵活;与单个延时负反馈回路相比，它可以在更宽的刺激范围内产生鲁棒的大幅度振荡。此外，系统的可调谐性主要取决于耦合反馈回路的拓扑结构，而较少依赖于模型组件之间的确切参数值或交互模式。因此，我们的研究结果解释了为什么这样的系统代表一个可调的主题，并可以完成各种功能。这些也表明，耦合反馈回路可以作为合成生物学中设计各种功能电路的工具箱。
Positive and negative feedback loops are often coupled to perform various functions in gene regulatory networks, acting as bistable switches, oscillators, and excitable devices. It is implied that such a system with interlinked positive and negative feedback loops is a flexible motif that can modulate itself among various functions. Here, we developed a minimal model for the system and systematically explored its dynamics and performance advantage in response to stimuli in a unifying framework. The system indeed displays diverse behaviors when the strength of feedback loops is changed. First, the system can be tunable from monostability to bistability by increasing the strength of positive feedback, and the bistability regime is modulated by the strength of negative feedback. Second, the system undergoes transitions from bistability to excitability and to oscillation with increasing the strength of negative feedback, and the reverse conversion occurs by enhancing the strength of positive feedback. Third, the system is more flexible than a single feedback loop; it can produce robust larger-amplitude oscillations over a wider stimulus regime compared with a single time-delayed negative feedback loop. Furthermore, the tunability of the system depends mainly on the topology of coupled feedback loops but less on the exact parameter values or the mode of interactions between model components. Thus, our results interpret why such a system represents a tunable motif and can accomplish various functions. These also suggest that coupled feedback loops can act as toolboxes for engineering diverse functional circuits in synthetic biology.