The expression of enhancer RNAs (eRNAs) is important for enhancer activation. As eRNAs are non-polyadenylated, Shiekhattar and colleagues studied the role of the Integrator complex, which is required for the 3′-end processing of other non-polyadenylated RNAs, in their biogenesis. They found that addition of epidermal growth factor (EGF) to HeLa cells resulted in Integrator recruitment to EGF-responsive enhancers and the induction of eRNA expression. When the Integrator subunit INTS11 was depleted, unprocessed eRNAs accumulated, the formation of EGF-dependent interactions between enhancers and promoters was abrogated, and the expression of EGF-responsive genes was reduced. The ectopic expression of wild-type, but not catalytically inactive, INTS11 restored EGF-dependent eRNA and gene expression, indicating that defects in eRNA processing contribute to the loss of transcriptional responsiveness to signalling cues.
References
Lai, F. et al. Integrator mediates the biogenesis of enhancer RNAs. Nature http://dx.doi.org/10.1038/nature14906 (2015)
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Zlotorynski, E. Integrator enhances enhancers. Nat Rev Mol Cell Biol 16, 579 (2015). https://doi.org/10.1038/nrm4060
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DOI: https://doi.org/10.1038/nrm4060