Transcription Factor Activity Mapping of a Tissue-Specific in vivo Gene Regulatory Network.
Transcription Factor Activity Mapping of a Tissue-Specific in vivo Gene Regulatory Network.
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DOI：
10.1016/j.cels.2015.08.003
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发表时间：
2015-08-26
期刊：
影响因子：
9.3
通讯作者：
Walhout AJ
中科院分区：
文献类型：
--
作者：
MacNeil LT;Pons C;Arda HE;Giese GE;Myers CL;Walhout AJ
转录因子 (TF) 和 DNA 之间的大量物理相互作用数据已经产生，但这些相互作用通常不会产生明显的监管后果。因此，将物理相互作用数据与基因调控网络（GRN）等同起来是有问题的。在这里，我们全面测定 TF 活性，而不是结合，以构建秀丽隐杆线虫肠道中的基因调控相互作用网络。通过手动观察一组 19 个荧光转录报告基因上 921 个 TF 的体内组织特异性敲低，我们确定了 19 个启动子和 177 个 TF 之间的 411 个相互作用的 GRN。该 GRN 仅显示与物理相互作用的适度重叠，表明许多监管相互作用是间接的。我们应用嵌套效应模型来揭示肠道中 TF 之间的信息流，这些信息流汇聚于一小组物理 TF-启动子相互作用。我们发现了许多细胞非自主调节相互作用，说明了组织间的通讯。总而言之，我们的研究阐明了活体动物中基因调控的复杂性。
A wealth of physical interaction data between transcription factors (TFs) and DNA has been generated, but these interactions often do not have apparent regulatory consequences. Thus, equating physical interaction data with gene regulatory networks (GRNs) is problematic. Here, we comprehensively assay TF activity, rather than binding, to construct a network of gene regulatory interactions in the C. elegans intestine. By manually observing the in vivo tissue-specific knockdown of 921 TFs on a panel of 19 fluorescent transcriptional reporters, we identified a GRN of 411 interactions between 19 promoters and 177 TFs. This GRN shows only modest overlap with physical interactions, indicating that many regulatory interactions are indirect. We applied nested effects modeling to uncover information flow between TFs in the intestine that converges on a small set of physical TF-promoter interactions. We found numerous cell nonautonomous regulatory interactions, illustrating tissue-to-tissue communication. Altogether, our study illuminates the complexity of gene regulation in the context of a living animal.