Open AccessTissue-Specific RNA Expression Marks Distant-Acting Developmental Enhancers
Author(s) -
Han Wu,
Alexander Nord,
Jennifer A. Akiyama,
Malak Shoukry,
Veena Afzal,
Edward M. Rubin,
Len A. Pennacchio,
Axel Visel
Publication year - 2014
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1004610
Subject(s) - enhancer , enhancer rnas , biology , transcriptome , gene expression , rna , regulation of gene expression , epigenomics , transcription (linguistics) , non coding rna , genetics , gene , transcription factor , computational biology , microbiology and biotechnology , dna methylation , linguistics , philosophy
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.