Enhancer RNA profiling predicts transcription factor activity.
Enhancer RNA profiling predicts transcription factor activity.
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DOI：
10.1101/gr.225755.117
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发表时间：
2018-03-01
期刊：
影响因子：
7
通讯作者：
Dowell RD
中科院分区：
文献类型：
--
作者：
Azofeifa JG;Allen MA;Hendrix JR;Read T;Rubin JD;Dowell RD
转录因子通过与增强子的结合发挥调控作用，协调基因表达程序。活性增强子的特征通常在于存在称为增强子RNA（eRNA）的短的、不稳定的转录物。虽然它们的功能尚不清楚，但我们证明eRNA是TF活性的强大读出器。我们在数百个公开的新生转录数据集上推断eRNA起源的位点，并表明eRNA起始于TF结合的位点。通过量化TF结合基序实例和eRNA来源的共定位，我们推导出一个简单的统计能够推断TF活性。在这样做的过程中，我们发现了几十个以前未探索的不同刺激和它们影响的TF之间的联系。
Transcription factors (TFs) exert their regulatory influence through the binding of enhancers, resulting in coordination of gene expression programs. Active enhancers are often characterized by the presence of short, unstable transcripts termed enhancer RNAs (eRNAs). While their function remains unclear, we demonstrate that eRNAs are a powerful readout of TF activity. We infer sites of eRNA origination across hundreds of publicly available nascent transcription data sets and show that eRNAs initiate from sites of TF binding. By quantifying the colocalization of TF binding motif instances and eRNA origins, we derive a simple statistic capable of inferring TF activity. In doing so, we uncover dozens of previously unexplored links between diverse stimuli and the TFs they affect.