Abstract
Enhancers are distal regulatory elements that mediate tissue‐ and temporal‐specific gene expression during development. Recent evidence has revealed that active enhancers are transcribed and that such enhancer RNAs (eRNAs) play an important role in transcriptional activation. We show that the metazoan‐specific RNA polymerase II (RNAPII)‐associated complex, Integrator, is recruited to enhancers and super‐enhancers in a stimulus‐dependent manner. Functional depletion of Integrator subunits diminished the signal‐dependent induction of eRNAs at enhancers and super‐enhancers. Global nuclear run‐on and RNAPII profiling demonstrated that Integrator regulates the maturation (3′‐end processing) of eRNAs. We show that the production of mature eRNAs require the catalytic activity of Integrator complex. We propose a role for Integrator in biogenesis of eRNAs in metazoans.
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