title: Tissue-specific RNA expression marks distant-acting developmental enhancers.
abstract: Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs) within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs) displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks.
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Nord
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Akiyama
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Malak
authors.initials: M
authors.lastname: Shoukry
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Veena
authors.initials: V
authors.lastname: Afzal
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America; U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America; U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America.
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
authors.affiliation: Lawrence Berkeley National Laboratory, Berkeley, California, United States of America; U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, United States of America; School of Natural Sciences, University of California, Merced, California, United States of America.
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
mesh_terms: D000818:Animals; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D023281:Genomics / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D015203:Reproducibility of Results; D014158:Transcription, Genetic
chemical_list: D022661:RNA, Untranslated