生物钟模型中的蛋白质隔离与Hill型抑制
Protein sequestration versus Hill-type repression in circadian clock models
摘要：
生物钟是一种自我维持的内源性振荡器，生物体通过它来跟踪每天和季节的时间。生物钟经常依赖于互锁的转录-翻译反馈回路来产生对内在和外在扰动稳健的节律。为了研究生物钟中细胞内反馈回路的动力学和机制，已经建立了许多数学模型。大多数模型使用希尔函数来描述转录抑制的方式是类似的古德温模型。最近，引入了一类新的基于蛋白质螯合的阻遏模型。在这里，我们讨论了这类新的模型显着不同于那些基于希尔型镇压在几个基本方面：节奏生成的条件，强大的网络设计和耦合振荡器的周期。一致的，这些基本性质的生物钟也不同脉孢菌，果蝇，和哺乳动物取决于其关键的转录抑制机制（希尔型抑制或蛋白质螯合）。本文从理论和实验两个方面综述了分子生物钟中转录抑制机制模型的重要性。
英文摘要：
Circadian (~24hr) 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, we discuss 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 modeling of transcriptional repression mechanisms in molecular circadian clocks.
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