Tissue-Specific RNA Expression Marks Distant-Acting Developmental Enhancers

Han Wu, Alexander Nord, Jennifer A. Akiyama, Malak Shoukry, Veena Afzal, Edward M. Rubin, Len A. Pennacchio, Axel Visel

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52 Scopus citations

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.

Original languageEnglish (US)
JournalPLoS Genetics
Volume10
Issue number9
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Wu, H., Nord, A., Akiyama, J. A., Shoukry, M., Afzal, V., Rubin, E. M., Pennacchio, L. A., & Visel, A. (2014). Tissue-Specific RNA Expression Marks Distant-Acting Developmental Enhancers. PLoS Genetics, 10(9). https://doi.org/10.1371/journal.pgen.1004610