Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.
Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.
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DOI：
10.1186/1752-0509-5-111
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发表时间：
2011-07-12
影响因子：
--
通讯作者：
Alon U
中科院分区：
文献类型：
--
作者：
Madar D;Dekel E;Bren A;Alon U
基因调控网络由反复出现的调控模式组成，称为网络基序。最常见的网络基序之一是负自动调节，其中转录因子抑制其自身的产生。负自调节有几个潜在的功能：它可以缩短响应时间（达到稳态一半的时间），稳定对噪声的表达，线性化基因的输入-输出响应曲线。后一种负自调节功能，增加了下游基因响应的输入信号范围，已经通过理论和合成基因电路进行了研究。在这里，我们要问的是，在自然系统的背景下，负自动调节是否也保留了这一功能，在自然系统中，它被嵌入到许多额外的相互作用中。为了解决这个问题，我们研究了大肠杆菌阿拉伯糖利用系统中的负自调节基序，其中负自调节是复杂调控网络的一部分。我们发现，当通过将调节因子araC置于本构表达下而破坏负自调节时，阿拉伯糖系统的输入动态范围减少了10倍。感应曲线的表观Hill系数从负自调节时的约n = 1变化到自调节中断时的约n = 2。我们提出了一个数学模型，该模型描述了负自调节如何通过将转录因子蛋白水平与输入信号耦合来增加输入动态范围。在这里，我们证明了大肠杆菌天然阿拉伯糖系统中的负自调节基序增加了系统可以响应的阿拉伯糖信号范围。这样，负自调节可能有助于增加输入动态范围，同时保持合作调节系统的特异性。这一功能可能有助于解释生物系统中常见的负自我调节现象。
Gene regulation networks are made of recurring regulatory patterns, called network motifs. One of the most common network motifs is negative auto-regulation, in which a transcription factor represses its own production. Negative auto-regulation has several potential functions: it can shorten the response time (time to reach halfway to steady-state), stabilize expression against noise, and linearize the gene's input-output response curve. This latter function of negative auto-regulation, which increases the range of input signals over which downstream genes respond, has been studied by theory and synthetic gene circuits. Here we ask whether negative auto-regulation preserves this function also in the context of a natural system, where it is embedded within many additional interactions. To address this, we studied the negative auto-regulation motif in the arabinose utilization system of Escherichia coli, in which negative auto-regulation is part of a complex regulatory network. We find that when negative auto-regulation is disrupted by placing the regulator araC under constitutive expression, the input dynamic range of the arabinose system is reduced by 10-fold. The apparent Hill coefficient of the induction curve changes from about n = 1 with negative auto-regulation, to about n = 2 when it is disrupted. We present a mathematical model that describes how negative auto-regulation can increase input dynamic-range, by coupling the transcription factor protein level to the input signal. Here we demonstrate that the negative auto-regulation motif in the native arabinose system of Escherichia coli increases the range of arabinose signals over which the system can respond. In this way, negative auto-regulation may help to increase the input dynamic-range while maintaining the specificity of cooperative regulatory systems. This function may contribute to explaining the common occurrence of negative auto-regulation in biological systems.
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DOI：
10.1016/0304-4165(66)90169-3
发表时间：
1966-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
NOVOTNY, CP;ENGLESBERG, E
通讯作者：
ENGLESBERG, E
影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
9.9
作者：
Dublanche, Yann;Michalodimitrakis, Konstantinos;Serrano, Luis
通讯作者：
Serrano, Luis
影响因子：
64.8
作者：
Austin, DW;Allen, MS;Simpson, ML
通讯作者：
Simpson, ML
影响因子：
3.5
作者：
Cormack, BP;Valdivia, RH;Falkow, S
通讯作者：
Falkow, S