Enhancers as non-coding RNA transcription units: recent insights and future perspectives

Nat Rev Genet. 2016 Apr;17(4):207-23. doi: 10.1038/nrg.2016.4. Epub 2016 Mar 7.


Networks of regulatory enhancers dictate distinct cell identities and cellular responses to diverse signals by instructing precise spatiotemporal patterns of gene expression. However, 35 years after their discovery, enhancer functions and mechanisms remain incompletely understood. Intriguingly, recent evidence suggests that many, if not all, functional enhancers are themselves transcription units, generating non-coding enhancer RNAs. This observation provides a fundamental insight into the inter-regulation between enhancers and promoters, which can both act as transcription units; it also raises crucial questions regarding the potential biological roles of the enhancer transcription process and non-coding enhancer RNAs. Here, we review research progress in this field and discuss several important, unresolved questions regarding the roles and mechanisms of enhancers in gene regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation
  • Genomic Instability
  • Humans
  • Models, Genetic
  • Multigene Family
  • Promoter Regions, Genetic
  • RNA Processing, Post-Transcriptional
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • RNA, Untranslated
  • Transcription Factors