A mathematical model for the Kai-protein-based chemical oscillator and clock gene expression rhythms in cyanobacteria
A mathematical model for the Kai-protein-based chemical oscillator and clock gene expression rhythms in cyanobacteria
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DOI：
10.1177/0748730406295749
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发表时间：
2007-02-01
影响因子：
3.5
通讯作者：
Tomita, Masaru
中科院分区：
文献类型：
--
作者：
Miyoshi, Fumihiko;Nakayama, Yoichi;Tomita, Masaru
在蓝藻细长聚球藻中，大多数启动子在连续光 (LL) 条件下受到生物钟的调节。然而，基本的昼夜节律振荡主要是由翻译后水平上交替的 KaiC 磷酸化/去磷酸化反应产生的。事实上，最近通过将 KaiA、KaiB 和 KaiC 蛋白与 ATP 一起孵育，在体外重建了 KaiC 磷酸化循环。然而，这种化学振荡的分子动力学和驱动昼夜节律转录/翻译节律的机制仍然未知。在本报告中，对蓝藻昼夜节律系统中的 KaiC 磷酸化循环和基因调控网络进行了建模。该模型再现了体外观察到的在缺乏从头基因表达的情况下强大的 KaiC 磷酸化循环，以及其与体内 LL 条件下的转录/翻译反馈的耦合。此外，该模型与之前的大多数实验一致，包括基因敲除或kai基因过度表达的各种组合。它还预测蓝藻昼夜节律系统可能需要多个 KaiC 磷酸化状态和动态 Kai 蛋白相互作用。
In the cyanobacterium, Synechococcus elongatus, most promoters are regulated by a circadian clock under continuous light (LL) conditions. Nevertheless, the basic circadian oscillation is primarily generated by alternating KaiC phosphorylation/dephosphorylation reactions at the posttranslational level. Indeed, the KaiC phosphorylation cycle was recently reconstituted in vitro by incubating KaiA, KaiB, and KaiC proteins with ATP. However, the molecular dynamics of this chemical oscillation and the mechanism that drives the circadian transcription/translation rhythms remain unknown. In this report, the KaiC phosphorylation cycle and the gene regulatory network in the cyanobacterial circadian system have been modeled. The model reproduces the robust KaiC phosphorylation cycle in the absence of de novo gene expression as is observed in vitro, as well as its coupling to transcriptional/translational feedback in LL conditions in vivo. Moreover, the model is consistent with most previous experiments, including various combinations of genetic knockout or overexpression of kai genes. It also predicts that multiple KaiC phosphorylation states and dynamic Kai protein interactions may be required for the cyanobacterial circadian system.