Mangan S, Itzkovitz S, Zaslaver A, Alon U
Department of Molecular Cell Biology and Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel.
J Mol Biol. 2006 Mar 10;356(5):1073-81. doi: 10.1016/j.jmb.2005.12.003. Epub 2005 Dec 19.
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.
复杂的基因调控网络由称为网络基序的简单重复基因回路组成。最常见的网络基序之一是1型非相干前馈环(I1-FFL),其中转录激活因子直接激活一个基因,同时也激活该基因的一个阻遏物。数学建模表明,I1-FFL可以表现出两种动力学特征:基因表达的瞬态脉冲,以及目标基因动力学的加速。在活细胞中对这种基序的动力学进行实验研究很重要,以测试它即使嵌入细胞内的其他相互作用中是否仍能执行这些功能。在这里,我们使用具有非相干前馈环连接性的系统——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,以高时间分辨率和精度测量了该系统对诱导信号的动力学响应。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的菌株和条件下,这种加速被消除。半乳糖系统中的I1-FFL基序尽管嵌入了几个额外的反馈回路,但仍如理论预测的那样发挥作用。响应加速可能由从细菌到人类的各种系统中发现的非相干前馈环模块执行。