Title: A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer
Author: Han Chen, Han Liang
Abstract: Although enhancers play critical roles in cancer, quantifying enhancer activitiesin clinical samples remains challenging, especially for super-enhancers. Enhanceractivities can be inferred from enhancer RNA (eRNA) signals, which requires enhancertranscription loci definition. Only a small proportion of human eRNA loci has beenprecisely identified, limiting investigations of enhancer-mediated oncogenic mechanisms.Here, we characterize super-enhancer regions using aggregated RNA sequencing (RNA-seq)data from large cohorts. Super-enhancers usually contain discrete loci featuring sharpeRNA expression peaks. We identify >300,000 eRNA loci in ～377 Mb super-enhancer regionsthat are regulated by evolutionarily conserved, well-positioned nucleosomes and arefrequently dysregulated in cancer. The eRNAs provide explanatory power for cancerphenotypes beyond that provided by mRNA expression through resolving intratumoralheterogeneity with enhancer cell-type specificity. Our study provides a high-resolutionmap of eRNA loci through which super-enhancer activities can be quantified by RNA-seqand a user-friendly data portal, enabling a broad range of biomedical investigations.