Spirits in the Material World: Enhancer RNAs in Transcriptional Regulation

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 pause-release to regulate gene expression.