Deciphering the transcriptional regulatory logic of amino acid metabolism.
Deciphering the transcriptional regulatory logic of amino acid metabolism.
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DOI：
10.1038/nchembio.710
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发表时间：
2011-11-13
影响因子：
14.8
通讯作者：
Palsson, Bernhard O.
中科院分区：
文献类型：
--
作者：
Cho, Byung-Kwan;Federowicz, Stephen;Park, Young-Seoub;Zengler, Karsten;Palsson, Bernhard O.
尽管代谢网络已经在基因组规模上重建，但转录调控网络的相应重建和整合尚未完全实现。在这里，我们重建了大肠杆菌氨基酸代谢的集成网络。对转录因子 ArgR、Lrp 和 TrpR 的 ChIP 芯片和基因表达数据的分析表明，它们调节的基因中约 82% 直接参与氨基酸代谢。进一步分析表明，19/20氨基酸生物合成途径直接或间接受这三个转录因子控制。将调控基因分为运输、生物合成和代谢三个功能类别，从而阐明构成整合网络基本构件的调控基序。这些基序的调控逻辑是根据转录因子结合与响应外源氨基酸的转录水平变化之间的关系确定的。值得注意的是，由此产生的逻辑显示了氨基酸如何区分为信号分子和营养分子，从而揭示了这种刺激的总体调节原理。
Although metabolic networks have been reconstructed on a genome-scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and gene expression data for the transcription factors ArgR, Lrp, and TrpR showed that ∼82% of the genes they regulate are directly involved in amino acid metabolism. Further analysis shows that 19/20 amino acid biosynthetic pathways are either directly or indirectly controlled by these three transcription factors. Classifying the regulated genes into three functional categories of transport, biosynthesis, and metabolism leads to elucidation of regulatory motifs constituting the integrated network's basic building blocks. The regulatory logic of these motifs was determined based on the relationships between transcription factor binding and changes in transcript levels in response to exogenous amino acids. Remarkably, the resulting logic shows how amino acids are differentiated as signaling and nutrient molecules, and thus revealing the overarching regulatory principles of this stimulon.
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影响因子：
46.9
作者：
Cho, Byung-Kwan;Zengler, Karsten;Qiu, Yu;Park, Young Seoub;Knight, Eric M.;Barrett, Christian L.;Gao, Yuan;Palsson, Bernhard O.
通讯作者：
Palsson, Bernhard O.
影响因子：
5.6
作者：
MAAS, WK;CLARK, AJ
通讯作者：
CLARK, AJ
DOI：
10.1073/pnas.0807227105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Cho, Byung-Kwan;Barrett, Christian L.;Palsson, Bernhard O.
通讯作者：
Palsson, Bernhard O.
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y