Enhancer RNA profiling predicts transcription factor activity

被引:79
作者
Azofeifa, Joseph G. [1 ,2 ]
Allen, Mary A. [2 ]
Hendrix, Josephina R. [1 ,3 ]
Read, Timothy [2 ,4 ]
Rubin, Jonathan D. [4 ]
Dowell, Robin D. [1 ,2 ,3 ]
机构
[1] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA
[2] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA
[3] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
[4] Univ Colorado, Dept Biochem, Boulder, CO 80309 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
BINDING SITES MODELS; HUMAN CELL-TYPES; GENE-EXPRESSION; POLYMERASE-II; REGULATORY ELEMENTS; MAMMALIAN PROMOTERS; MYELOID-LEUKEMIA; ACTIVATION; PROTEIN; DIFFERENTIATION;
D O I
10.1101/gr.225755.117
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:334 / 344
页数:11
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