Kim Jae Kyoung
Department of Mathematical Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro Yuseong-gu, Daejeon, 34141, Korea.
IET Syst Biol. 2016 Aug;10(4):125-35. doi: 10.1049/iet-syb.2015.0090.
Circadian (∼24 h) clocks are self-sustained endogenous oscillators with which organisms keep track of daily and seasonal time. Circadian clocks frequently rely on interlocked transcriptional-translational feedback loops to generate rhythms that are robust against intrinsic and extrinsic perturbations. To investigate the dynamics and mechanisms of the intracellular feedback loops in circadian clocks, a number of mathematical models have been developed. The majority of the models use Hill functions to describe transcriptional repression in a way that is similar to the Goodwin model. Recently, a new class of models with protein sequestration-based repression has been introduced. Here, the author discusses how this new class of models differs dramatically from those based on Hill-type repression in several fundamental aspects: conditions for rhythm generation, robust network designs and the periods of coupled oscillators. Consistently, these fundamental properties of circadian clocks also differ among Neurospora, Drosophila, and mammals depending on their key transcriptional repression mechanisms (Hill-type repression or protein sequestration). Based on both theoretical and experimental studies, this review highlights the importance of careful modelling of transcriptional repression mechanisms in molecular circadian clocks.
昼夜节律（约24小时）时钟是自我维持的内源性振荡器，生物体借此追踪每日和季节性时间。昼夜节律时钟常常依靠相互连锁的转录-翻译反馈环来产生对内在和外在干扰具有稳健性的节律。为了研究昼夜节律时钟中细胞内反馈环的动力学和机制，已经开发了许多数学模型。大多数模型使用希尔函数来描述转录抑制，其方式类似于古德温模型。最近，引入了一类基于蛋白质隔离抑制的新模型。在此，作者讨论了这类新模型在几个基本方面与基于希尔型抑制的模型有何显著不同：节律产生的条件、稳健的网络设计以及耦合振荡器的周期。同样，昼夜节律时钟的这些基本特性在脉孢菌、果蝇和哺乳动物之间也因它们关键的转录抑制机制（希尔型抑制或蛋白质隔离）而有所不同。基于理论和实验研究，本综述强调了在分子昼夜节律时钟中对转录抑制机制进行仔细建模的重要性。
