Multiple functions of a feed-forward-loop gene circuit.
Multiple functions of a feed-forward-loop gene circuit.
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DOI：
10.1016/j.jmb.2005.04.022
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发表时间：
2005-06
影响因子：
5.6
通讯作者：
M. Wall;M. Dunlop;W. Hlavacek
中科院分区：
文献类型：
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作者：
M. Wall;M. Dunlop;W. Hlavacek
前馈环（FFL）是基因调控网络中的一个网络基序，它涉及两个转录因子：一个调节第二个转录因子的表达，两个转录因子都调节一个效应基因的表达。FFL设计原则的分析已经开始，但FFL的功能意义仍然不清楚。在目前的理论研究中，普遍认为传递函数与不同的信号相互作用。然而，我们在大肠杆菌中发现了FFL的例子，其中两个TF与相同的信号相互作用。这些例子属于FFL的2型不相干类别，其中每个TF专门充当转录阻遏物。在这里，我们分析这类电路的数学模型，检查一个全面的数组的子类，不同的信号调制的TF的活动。通过参数的变化，我们统计特征如何输入/输出（I/O）的行为和时间响应性预测依赖于电路中的信号相互作用的布线。我们发现，电路可以表现出任何13个定性不同的稳态I/O模式，包括诱导和抑制模式。一些子类显示多达六种模式。瞬态脉冲也是可能的，电路对信号的响应可能比只有一个TF的基因电路更快或更慢。我们的结果提供了一类FFL电路的功能目录，其子类具有不同的可能行为的宽度和不同的典型行为。
The feed-forward-loop (FFL), a network motif in genetic regulatory networks, involves two transcription factors (TFs): one regulates the expression of the second, and both TFs regulate the expression of an effector gene. Analysis of FFL design principles has been initiated, but the functional significance of the FFL is still unclear. In theoretical studies so far, the TFs are assumed to interact with different signals, which is common. However, we have found examples of FFLs in Escherichia coli in which both TFs interact with the same signal. These examples belong to the type 2 incoherent class of FFLs, in which each TF acts exclusively as a repressor of transcription. Here, we analyze mathematical models of this class of circuits, examining a comprehensive array of subclasses that differ in the way a signal modulates the activities of the TFs. Through parameter variation, we characterize statistically how input/output (I/O) behavior and temporal responsiveness are predicted to depend on the wiring of signal interactions in a circuit. We find that circuits can exhibit any of 13 qualitatively distinct steady-state I/O patterns, including inducible and repressible patterns. Some subclasses exhibit as many as six patterns. Transient pulses are also possible, and the response of a circuit to a signal may be either faster or slower than that of a gene circuit in which there is only one TF. Our results provide a catalog of functions for a class of FFL circuits, whose subclasses have different breadths of possible behaviors and different typical behaviors.