4.6 Review

Spirits in the Material World: Enhancer RNAs in Transcriptional Regulation

Journal

TRENDS IN BIOCHEMICAL SCIENCES
Volume 46, Issue 2, Pages 138-153

Publisher

CELL PRESS
DOI: 10.1016/j.tibs.2020.08.007

Keywords

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Funding

  1. National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK058110]
  2. Cancer Prevention and Research Institute of Texas (CPRIT) [RP160318, RP190235]
  3. Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment

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Recent studies have shown that enhancer RNAs (eRNAs) play functional roles in activating gene expression, rather than just being non-functional byproducts of nearby transcription machinery. Challenges in elucidating the functions of eRNAs lie in their unstable nature and limitations of knockdown approaches.
Responses to developmental and environmental cues depend on precise spatiotemporal control of gene transcription. Enhancers, which comprise DNA elements bound by regulatory proteins, can activate target genes in response to these external signals. Recent studies have shown that enhancers are transcribed to produce enhancer RNAs (eRNAs). Do eRNAs play a functional role in activating gene expression or are they non-functional byproducts of nearby transcription machinery? The unstable nature of eRNAs and over-reliance on knockdown approaches have made elucidating the possible functions of eRNAs challenging. We focus here on studies using cloned eRNAs to study their function as transcripts, revealing roles for eRNAs in enhancer-promoter looping, recruiting transcriptional machinery, and facilitating RNA polymerase pauserelease to regulate gene expression.

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