Ultrasensitivity and noise propagation in a synthetic transcriptional cascade
Ultrasensitivity and noise propagation in a synthetic transcriptional cascade
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DOI：
10.1073/pnas.0408507102
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发表时间：
2005-03-08
影响因子：
11.1
通讯作者：
Weiss, R
中科院分区：
文献类型：
--
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通过生物网络的信息流的精确性质，这是由诸如响应灵敏度和噪声传播等因素决定的，极大地影响了生物系统的运行。这些性质的定量分析在自然发生的系统中往往是困难的，但可以通过研究简单的合成网络大大方便。在这里，我们报告的合成转录级联的建设，包括一个，两个和三个镇压阶段。这些模型系统使我们能够分析灵敏度和噪声传播作为网络复杂性的函数。我们证明实验稳态切换行为，变得更尖锐的级联较长。根据系统的输入条件，赋予这种超灵敏反应的调节机制既减弱又放大表型变化。虽然噪声衰减允许级联通过拒绝输入条件中的短暂扰动而充当低通滤波器，但噪声放大导致细胞群体之间的同步性丧失。证明上述网络特性的实验结果与系统简单数学模型的模拟具有良好的相关性。
The precise nature of information flow through a biological network, which is governed by factors such as response sensitivities and noise propagation, greatly affects the operation of biological systems. Quantitative analysis of these properties is often difficult in naturally occurring systems but can be greatly facilitated by studying simple synthetic networks. Here, we report the construction of synthetic transcriptional cascades comprising one, two, and three repression stages. These model systems enable us to analyze sensitivity and noise propagation as a function of network complexity. We demonstrate experimentally steady-state switching behavior that becomes sharper with longer cascades. The regulatory mechanisms that confer this ultrasensitive response both attenuate and amplify phenotypical variations depending on the system's input conditions. Although noise attenuation allows the cascade to act as a low-pass filter by rejecting short-lived perturbations in input conditions, noise amplification results in loss of synchrony among a cell population. The experimental results demonstrating the above network properties correlate well with simulations of a simple mathematical model of the system.