Systems analysis of transcription factor activities in environments with stable and dynamic oxygen concentrations.
Systems analysis of transcription factor activities in environments with stable and dynamic oxygen concentrations.
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DOI：
10.1098/rsob.120091
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发表时间：
2012-07
期刊：
影响因子：
5.8
通讯作者：
SysMO-SUMO Consortium
中科院分区：
文献类型：
--
作者：
Rolfe MD;Ocone A;Stapleton MR;Hall S;Trotter EW;Poole RK;Sanguinetti G;Green J;SysMO-SUMO Consortium
了解基因调控需要了解转录因子(TF)活性的变化。目前还不可能同时直接测量许多转移因子的活动。然而，推断TF活动的统计方法已经产生了对单个TF的不平凡和可验证的预测。在这里，全球统计模型确定了在稳定(固定氧气可获得性)和动态(氧气可获得性变化)环境中生长的大肠杆菌转录本的转铁蛋白活性的变化。确定了一个核心的氧响应因子网络，并补充了在特定条件下作用的附加因子。细胞质氧反应因子Tf、FNR和膜结合末端氧化酶的活性表明，即使在细菌细胞的尺度上，空间效应也显著影响氧感觉。几个转录本在有氧到厌氧以及厌氧到有氧的转变中表现出不对称的丰度模式。其中一个转录本NDH编码有氧呼吸链的一个主要组成部分，受氧响应因子Arca和FNR的调控。动力学模拟表明，Arca和FNR的行为不能解释NDH转录谱，导致另一种转铁蛋白PdhR被确定为不对称的来源。因此，这种方法说明了对稳定和动态环境中的监管反应进行系统检查是如何产生对适应过程的新的机械性见解的。
Understanding gene regulation requires knowledge of changes in transcription factor (TF) activities. Simultaneous direct measurement of numerous TF activities is currently impossible. Nevertheless, statistical approaches to infer TF activities have yielded non-trivial and verifiable predictions for individual TFs. Here, global statistical modelling identifies changes in TF activities from transcript profiles of Escherichia coli growing in stable (fixed oxygen availabilities) and dynamic (changing oxygen availability) environments. A core oxygen-responsive TF network, supplemented by additional TFs acting under specific conditions, was identified. The activities of the cytoplasmic oxygen-responsive TF, FNR, and the membrane-bound terminal oxidases implied that, even on the scale of the bacterial cell, spatial effects significantly influence oxygen-sensing. Several transcripts exhibited asymmetrical patterns of abundance in aerobic to anaerobic and anaerobic to aerobic transitions. One of these transcripts, ndh, encodes a major component of the aerobic respiratory chain and is regulated by oxygen-responsive TFs ArcA and FNR. Kinetic modelling indicated that ArcA and FNR behaviour could not explain the ndh transcript profile, leading to the identification of another TF, PdhR, as the source of the asymmetry. Thus, this approach illustrates how systematic examination of regulatory responses in stable and dynamic environments yields new mechanistic insights into adaptive processes.
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DOI：
10.1073/pnas.0609514104
发表时间：
2007-02-13
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
3.2
作者：
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DOI：
10.1073/pnas.2136632100
发表时间：
2003-12-23
影响因子：
11.1
作者：
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通讯作者：
Roychowdhury, VP
影响因子：
14.9
作者：
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通讯作者：
Karp PD
影响因子：
5.8
作者：
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通讯作者：
Sanguinetti, Guido