National Laboratory of Solid State Microstructures, Department of Physics, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.
Center for Epigenomics, University of California, San Diego, La Jolla, CA 92093-0653, USA.
J Theor Biol. 2018 Dec 7;458:125-132. doi: 10.1016/j.jtbi.2018.09.013. Epub 2018 Sep 14.
The circadian clock regulates the expression of clock-controlled genes and adapts to environmental changes. Reactive oxygen species (ROS) also undergo circadian rhythms and have a role in circadian timekeeping. To elucidate crosstalk between ROS and the circadian clock in Neurospora crassa, we build an integrative network model, characterizing the circadian oscillator, ROS system and their interactions. Notably, the (de)phosphorylation and nuclear-cytoplasmic shuttling of clock proteins are modeled in detail. Simulation results quantitatively reproduce the essential features of circadian rhythm (both in constant darkness and under light/dark cycles) and the changes in period length and phase when ROS levels are altered under diverse conditions. This work clarifies the effects of three interactions between ROS and the clock on the circadian rhythm, suggesting that the regulation of WCC activity by protein phosphatase 2A in an O-dependent manner plays a predominant role. The functional significance of such modulations is also discussed.
生物钟调节时钟控制基因的表达，并适应环境变化。活性氧 (ROS) 也存在昼夜节律，并在生物钟计时中发挥作用。为了阐明 Neurospora crassa 中 ROS 和生物钟之间的串扰，我们构建了一个综合网络模型，该模型描述了生物钟振荡器、ROS 系统及其相互作用。值得注意的是，时钟蛋白的（去）磷酸化和核质穿梭被详细建模。模拟结果定量再现了生物钟节律的基本特征（在持续黑暗和光/暗循环下），以及在不同条件下改变 ROS 水平时周期长度和相位的变化。这项工作阐明了 ROS 和时钟之间的三种相互作用对生物钟节律的影响，表明蛋白磷酸酶 2A 以 O 依赖的方式调节 WCC 活性起着主要作用。还讨论了这种调节的功能意义。
