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Genome Res. 2018 Feb 15. doi: 10.1101/gr.225755.117. [Epub ahead of print]

Enhancer RNA profiling predicts transcription factor activity.

Author information

1
Department of Computer Science, University of Colorado, Boulder, Colorado 80309, USA.
2
BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
3
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
4
Department 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.

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