The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli
The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli
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DOI：
10.1016/j.jmb.2005.12.003
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发表时间：
2006-03-10
影响因子：
5.6
通讯作者：
Alon, U
中科院分区：
文献类型：
--
作者：
Mangan, S;Itzkovitz, S;Alon, U
复杂的基因调控网络由称为网络基序的简单重复基因电路组成。最常见的网络基序之一是不相干的 1 型前馈环 (I1-FFL)，其中转录激活子直接激活基因，同时也激活该基因的阻遏子。数学模型表明，I1-FFL 可以表现出两种动态特征：基因表达的瞬时脉冲和目标基因动态的加速。重要的是通过实验研究活细胞中该基序的动态，以测试即使嵌入到细胞中的额外相互作用中，它是否也能执行这些功能。在这里，我们使用具有不相干前馈环连接的系统，即大肠杆菌的半乳糖 (gal) 系统来解决这个问题。我们通过绿色荧光蛋白报告基因以高时间分辨率和准确性测量了该系统响应诱导信号的动态。我们表明半乳糖系统显示出加速的开启动力学。在破坏 I1-FFL 的应变和条件下，加速会被取消。尽管嵌入在几个额外的反馈环中，但 gal 系统中的 I1-FFL 基序按照理论预测的方式工作。响应加速可以通过不相干的前馈回路模块来执行，这些模块存在于从细菌到人类的各种系统中。 (c) 2005 Elsevier Ltd. 保留所有权利。
Complex gene regulation networks are made of simple recurring gene circuits called network motifs. One of the most common network motifs is the incoherent type-1 feed-forward loop (I1-FFL), in which a transcription activator activates a gene directly, and also activates a repressor of the gene. Mathematical modeling suggested that the I1-FFL can show two dynamical features: a transient pulse of gene expression, and acceleration of the dynamics of the target gene. It is important to experimentally study the dynamics of this motif in living cells, to test whether it carries out these functions even when embedded within additional interactions in the cell. Here, we address this using a system with incoherent feed-forward loop connectivity, the galactose (gal) system of Escherichia coli. We measured the dynamics of this system in response to inducing signals at high temporal resolution and accuracy by means of green fluorescent protein reporters. We show that the galactose system displays accelerated turn-on dynamics. The acceleration is abolished in strains and conditions that disrupt the I1-FFL. The I1-FFL motif in the gal system works as theoretically predicted despite being embedded in several additional feedback loops. Response acceleration may be performed by the incoherent feed-forward loop modules that are found in diverse systems from bacteria to humans. (c) 2005 Elsevier Ltd. All rights reserved.