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Epigenet Insights. 2019 May 7;12:2516865719846093. doi: 10.1177/2516865719846093. eCollection 2019.

Enhancer RNAs: Insights Into Their Biological Role.

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Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, México.


Enhancers play a central role in the transcriptional regulation of metazoans. Almost a decade ago, the discovery of their pervasive transcription into noncoding RNAs, termed enhancer RNAs (eRNAs), opened a whole new field of study. The presence of eRNAs correlates with enhancer activity; however, whether they act as functional molecules remains controversial. Here we review direct experimental evidence supporting a functional role of eRNAs in transcription and provide a general pipeline that could help in the design of experimental approaches to investigate the function of eRNAs. We propose that induction of transcriptional activity at enhancers promotes an increase in its activity by an RNA-mediated titration of regulatory proteins that can impact different processes like chromatin accessibility or chromatin looping. In a few cases, transcripts originating from enhancers have acquired specific molecular functions to regulate gene expression. We speculate that these transcripts are either nonannotated long noncoding RNAs (lncRNAs) or are evolving toward functional lncRNAs. Further work will be needed to comprehend better the biological activity of these transcripts.


chromatin; chromatin loop; eRNAs; enhancer; gene expression; lncRNAs

Conflict of interest statement

Declaration of conflicting interests:J.C.F.L. and R.G.A.M. are PhD students from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México. J.C-F.L. received fellowship 549543 from CONACyT, and R.G.A-M. received fellowships 288814 and 25590 from CONACyT.

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