A new tool for discovering transcriptional regulators of co-expressed genes predicts gene regulatory networks that mediate ethylene-controlled root development
A new tool for discovering transcriptional regulators of co-expressed genes predicts gene regulatory networks that mediate ethylene-controlled root development
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DOI：
10.1093/insilicoplants/diaa006
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发表时间：
2020-01-01
期刊：
影响因子：
3.1
通讯作者：
Muday, Gloria K.
中科院分区：
文献类型：
--
作者：
Harkey, Alexandria F.;Sims, Kira N.;Muday, Gloria K.
基因调控网络(GRN)是由一系列转录事件定义的，通过这些事件，激素或环境信号等信号改变发育。为了理解这些网络，有必要将特定的转录因子(TF)与其调控其表达的下游基因靶标联系起来。尽管多种方法提供了关于单个转运蛋白靶标的信息，但从一组共表达的基因转移到控制它们的转运蛋白是更加困难的。为了促进这种自下而上的方法，我们开发了一个名为TF Deacon的Web应用程序。该应用程序使用可公开获得的拟南芥DNA亲和纯化(DAP-Seq)数据集来搜索显示与共调控基因组的丰富结合的转录因子。我们使用高时间分辨率的转录数据集，使用TF Deacon检查了受乙烯前体1-氨基环丙烷-1-羧酸(ACC)处理调节的转录组。我们证明了当共调控基因根据反应时间或细胞类型特定信息进行划分时，这一应用程序的实用性，与使用定义较少且数量较大的共调控基因组时相比，这提供了更多关于TF/靶点关系的信息。这种方法预测了可能参与乙烯调控的根发育的转录因子，包括转录因子NAM(无顶端分生组织)。我们用遗传方法证明了NAM的突变减少了ACC对侧根发育的负调控。这里使用的过滤和Tf Deacon的组合可以应用于任何一组共同调节的基因，以预测控制协调转录反应的GRN。
Gene regulatory networks (GRNs) are defined by a cascade of transcriptional events by which signals, such as hormones or environmental cues, change development. To understand these networks, it is necessary to link specific transcription factors (TFs) to the downstream gene targets whose expression they regulate. Although multiple methods provide information on the targets of a single TF, moving from groups of co-expressed genes to the TF that controls them is more difficult. To facilitate this bottom-up approach, we have developed a web application named TF DEACoN. This application uses a publicly available Arabidopsis thaliana DNA Affinity Purification (DAP-Seq) data set to search for TFs that show enriched binding to groups of co-regulated genes. We used TF DEACoN to examine groups of transcripts regulated by treatment with the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), using a transcriptional data set performed with high temporal resolution. We demonstrate the utility of this application when co-regulated genes are divided by timing of response or cell-type-specific information, which provides more information on TF/target relationships than when less defined and larger groups of co-regulated genes are used. This approach predicted TFs that may participate in ethylene-modulated root development including the TF NAM (NO APICAL MERISTEM). We used a genetic approach to show that a mutation in NAM reduces the negative regulation of lateral root development by ACC. The combination of filtering and TF DEACoN used here can be applied to any group of co-regulated genes to predict GRNs that control coordinated transcriptional responses.