Enhancer RNA profiling predicts transcription factor activity
- Joseph G. Azofeifa1,2,
- Mary A. Allen2,
- Josephina R. Hendrix1,3,
- Timothy Read2,4,
- Jonathan D. Rubin4 and
- Robin D. Dowell1,2,3
- 1Department of Computer Science, University of Colorado, Boulder, Colorado 80309, USA;
- 2BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA;
- 3Department of Molecular, Cellular and Developmental Biology,
- 4Department of Biochemistry, University of Colorado, Boulder, Colorado 80309, USA
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.225755.117.
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Freely available online through the Genome Research Open Access option.
- Received May 30, 2017.
- Accepted January 24, 2018.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
