The co-regulation mechanism of transcription factors in the human gene regulatory network.

The co-regulation mechanism of transcription factors in the human gene regulatory network.
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DOI:
10.1093/nar/gks664
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发表时间:
2012-10
影响因子:
14.9
通讯作者:
Cho KH
Cho KH
中科院分区:
生物学2区
文献类型:
--
作者:
Kim J;Choi M;Kim JR;Jin H;Kim VN;Cho KH

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转录因子的共调控在许多物种中都有广泛的发现。为什么转录调控需要这样一种共调控机制?为了回答这个问题,进行了以下实验和分析。首先,人类基因调控网络(GRN)的检查表明,共调节显着丰富的人类GRN。其次,人工调控网络的数学模拟表明,共调节机制与TF的双相剂量-反应模式有关。第三,共调节机制和双相剂量反应模式之间的关系,证实了使用微阵列实验检查不同的时间点和不同剂量的有毒物质四氯二苯并二恶英。最后,我们构建了两个数学模型来模拟高度共调节网络(HCNs)和小共调节网络(LCNs),我们发现HCNs比LCNs对参数扰动更鲁棒,而LCNs比HCNs更快地适应环境变化。
The co-regulation of transcription factors (TFs) has been widely observed in various species. Why is such a co-regulation mechanism needed for transcriptional regulation? To answer this question, the following experiments and analyses were performed. First, examination of the human gene regulatory network (GRN) indicated that co-regulation was significantly enriched in the human GRN. Second, mathematical simulation of an artificial regulatory network showed that the co-regulation mechanism was related to the biphasic dose–response patterns of TFs. Third, the relationship between the co-regulation mechanism and the biphasic dose–response pattern was confirmed using microarray experiments examining different time points and different doses of the toxicant tetrachlorodibenzodioxin. Finally, two mathematical models were constructed to mimic highly co-regulated networks (HCNs) and little co-regulated networks (LCNs), and we found that HCNs were more robust to parameter perturbation than LCNs, whereas LCNs were faster in adaptation to environmental changes than HCNs.
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