Extracting regulator activity profiles by integration of de novo motifs and expression data: characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor.
Extracting regulator activity profiles by integration of de novo motifs and expression data: characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor.
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DOI：
10.1093/nar/gks205
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发表时间：
2012-07
影响因子：
14.9
通讯作者：
Burroughs NJ
中科院分区：
文献类型：
--
作者：
Iqbal M;Mast Y;Amin R;Hodgson DA;STREAM Consortium;Wohlleben W;Burroughs NJ
确定转录调节因子的活动是系统生物学的一个主要焦点，为调节机制和共同调节因子提供了关键的见解。对于像大肠杆菌这样的生物，转录调控因子结合位点数据可以与表达数据相结合来推断转录调控因子的活性。然而，对于大多数生物体来说，关于它们的转录调控因子的数据很少，而它们相关的结合基序在很大程度上是未知的。在这里，我们解决了通过生成新的(结合)基序并与表达数据集成来推断未知调节器的活动的挑战。我们确定了一些活跃在代谢开关中的关键调节因子，包括Phop及其相关的定向重复pho盒，两个SARP的候选基序，一个CRP家族调节因子，一个铁反应调节因子和LexA调节因子。使用凝胶位移分析获得了对我们的一些预测的实验验证。我们的分析适用于任何有合理数量的互补表达数据，并且其基序(过度表达或进化保守)可以在基因组中识别的有机体。
Determining transcriptional regulator activities is a major focus of systems biology, providing key insight into regulatory mechanisms and co-regulators. For organisms such as Escherichia coli, transcriptional regulator binding site data can be integrated with expression data to infer transcriptional regulator activities. However, for most organisms there is only sparse data on their transcriptional regulators, while their associated binding motifs are largely unknown. Here, we address the challenge of inferring activities of unknown regulators by generating de novo (binding) motifs and integrating with expression data. We identify a number of key regulators active in the metabolic switch, including PhoP with its associated directed repeat PHO box, candidate motifs for two SARPs, a CRP family regulator, an iron response regulator and that for LexA. Experimental validation for some of our predictions was obtained using gel-shift assays. Our analysis is applicable to any organism for which there is a reasonable amount of complementary expression data and for which motifs (either over represented or evolutionary conserved) can be identified in the genome.
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邮票：用于探索DNA结合基序相似性的网络工具。
影响因子：
14.9
作者：
Mahony, Shaun;Benos, Panayiotis V
通讯作者：
Benos, Panayiotis V
影响因子：
3.2
作者：
Hahn, JS;Oh, SY;Roe, JH
通讯作者：
Roe, JH
DOI：
10.1198/016214505000000187
发表时间：
2006-03-01
影响因子：
3.7
作者：
Heard, NA;Holmes, CC;Stephens, DA
通讯作者：
Stephens, DA
影响因子：
5.8
作者：
Mitragotri, Samir;Anissimov, Yuri G.;Roberts, Michael S.
通讯作者：
Roberts, Michael S.
DOI：
10.1073/pnas.112341999
发表时间：
2002-09-03
影响因子：
11.1
作者：
Li, H;Rhodius, V;Siggia, ED
通讯作者：
Siggia, ED