Rethinking transcriptional activation in the Arabidopsis circadian clock.
Rethinking transcriptional activation in the Arabidopsis circadian clock.
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DOI：
10.1371/journal.pcbi.1003705
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发表时间：
2014-07
影响因子：
4.3
通讯作者：
Troein C
中科院分区：
文献类型：
--
作者：
Fogelmark K;Troein C
昼夜节律钟是生物计时器，允许活细胞根据可预测的光线和其他环境因素的每日变化来计时其活动。高等植物生物钟的复杂性使得人们很难理解单个基因或分子相互作用的作用，数学建模在指导模式生物（如拟南芥）的生物钟研究方面很有用。我们提出了一个模型，在拟南芥中的生物钟，基于一个大的语料库发表的时间过程数据。从文献中的实验证据来看，时钟中的大多数相互作用都是压抑的。因此，我们删除了在该系统以前的模型中发现的所有转录激活，而是通过包括两个新的组件来扩展该系统，即早晨表达的激活剂RVE 8和夜间抑制剂/激活剂NOX。我们的建模结果表明，时钟不需要大量的激活剂，以重现所观察到的基因表达模式。例如，PRR基因的顺序表达不需要将基因连接为一系列激活剂。在所提出的模型中，转录激活完全是RVE 8的任务。RVE 8如何强烈影响其目标的预测被发现与早期的实验数据解释一致，但通常我们发现系统中的许多负反馈应该阻止对突变表型的直观解释。如果没有数学模型，时钟的动态很难预测，而且时钟最好被视为一个缠结的网络，而不是一系列的循环。像大多数生物一样，植物依赖阳光，进化赋予了它们一个内部时钟，通过它可以预测日出和日落。生物钟由许多基因组成，这些基因在一个复杂的网络中相互控制，导致蛋白质水平的每日振荡。基因之间的相互作用可以是积极的或消极的，导致靶基因被打开或关闭。通过构建数学模型，结合我们对该网络的了解，我们可以通过与模型结果进行比较来解释实验数据。实验数据和模型预测之间的任何差异都将突出我们缺乏理解的地方。我们从已发表的关于模式生物塔勒（Arabidopsis thaliana）生物钟的文章中收集了800多组测量数据。利用这些数据，我们构建了一个数学模型，与以前的模型相比，模拟时钟。我们使用我们的模型来研究基因之间的积极相互作用的作用，它们是否是时钟功能所必需的，以及它们是否可以在模型中识别。
Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops. Like most living organisms, plants are dependent on sunlight, and evolution has endowed them with an internal clock by which they can predict sunrise and sunset. The clock consists of many genes that control each other in a complex network, leading to daily oscillations in protein levels. The interactions between genes can be positive or negative, causing target genes to be turned on or off. By constructing mathematical models that incorporate our knowledge of this network, we can interpret experimental data by comparing with results from the models. Any discrepancy between experimental data and model predictions will highlight where we are lacking in understanding. We compiled more than 800 sets of measured data from published articles about the clock in the model organism thale cress (Arabidopsis thaliana). Using these data, we constructed a mathematical model which compares favourably with previous models for simulating the clock. We used our model to investigate the role of positive interactions between genes, whether they are necessary for the function of the clock and if they can be identified in the model.
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