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

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

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Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92037-0648, USA.


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.

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