Engineering stability in gene networks by autoregulation

Engineering stability in gene networks by autoregulation
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DOI:
10.1038/35014651
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发表时间:
2000-06-01
期刊:
影响因子:
64.8
通讯作者:
Serrano, L
Serrano, L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Becskei, A;Serrano, L

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遗传和生物化学网络是代谢稳态和活细胞发育程序的基础,它们必须能承受生物化学参数的相当大的变化和随机扰动(1-3)。这些作为瞬时变化发生,例如转录、翻译以及RNA和蛋白质降解。这些扰动的强度和持续时间在群体中的细胞之间不同(4)。细胞的独特状态,以及群体中的多样性,是由于单个细胞经历的不同环境刺激和生化过程的固有随机性(例如,参考文献5和6)。有人提出,但没有证明,基因回路中的自动调节负反馈回路提供了稳定性(7),从而限制了网络成分浓度波动的范围。在这里,我们已经设计并构建了简单的基因电路组成的一个调节器和转录抑制因子在大肠杆菌中的模块,我们表现出的稳定性产生的负反馈增益。
The genetic and biochemical networks which underlie such things as homeostasis in metabolism and the developmental programs of living cells, must withstand considerable variations and random perturbations of biochemical parameters(1-3). These occur as transient changes in, for example, transcription, translation, and RNA and protein degradation. The intensity and duration of these perturbations differ between cells in a population(4). The unique state of cells, and thus the diversity in a population, is owing to the different environmental stimuli the individual cells experience and the inherent stochastic nature of biochemical processes (for example, refs 5 and 6). It has been proposed, but not demonstrated, that autoregulatory, negative feedback loops in gene circuits provide stability(7), thereby limiting the range over which the concentrations of net-work components fluctuate. Here we have designed and constructed simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli and we show the gain of stability produced by negative feedback.