Abstract
Emerging evidence supports roles of enhancer RNAs (eRNAs) in regulating target gene. Here, we study eRNA regulation and function during skeletal myoblast differentiation. We provide a panoramic view of enhancer transcription and categorization of eRNAs. Master transcription factor MyoD is crucial in activating eRNA production. Super enhancer (se) generated seRNA-1 and -2 promote myogenic differentiation in vitro and in vivo. seRNA-1 regulates expression levels of two nearby genes, myoglobin (Mb) and apolipoprotein L6 (Apol6), by binding to heterogeneous nuclear ribonucleoprotein L (hnRNPL). A CAAA tract on seRNA-1 is essential in mediating seRNA-1/hnRNPL binding and function. Disruption of seRNA-1-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the Mb locus, in coincidence with the reduction of its transcription. Furthermore, analyses of hnRNPL binding transcriptome-wide reveal its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction represents a mechanism contributing to target mRNA activation.
Highlights
Emerging evidence supports roles of enhancer RNAs in regulating target gene
Using myoblast differentiation as a paradigm and seRNA-1 as an example, we dissected how it activated the transcription of target gene Mb through interacting with heterogeneous nuclear ribonucleoprotein L (hnRNPL) and modulating hnRNPL, polymerase II (Pol II), H3K36me[3] at Mb locus (Supplementary Fig. 12 and Supplementary Note 3)
Our findings suggest enhancer RNAs (eRNAs) binding to hnRNPL conveys a localized activity profile to the target chromatin, which is in agreement with several recent findings[18,19,47]
Summary
Emerging evidence supports roles of enhancer RNAs (eRNAs) in regulating target gene. We study eRNA regulation and function during skeletal myoblast differentiation. Super enhancer (se) generated seRNA-1 and -2 promote myogenic differentiation in vitro and in vivo. We propose that eRNA-hnRNPL interaction represents a mechanism contributing to target mRNA activation. We have solidified a pivotal role of myogenic differentiation protein (MyoD) in enhancer/SEs assembly and activation[6]. Li et al demonstrated that eRNAs can establish and/or stabilize chromatin looping between enhancers and promoters through interacting with components of mediator or cohesin complex[10,14]. A recent study revealed eRNA expressed from a distal enhancer of MyoD1 (DRReRNA) activates Myogenin expression in trans through interacting with cohesin complex[15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
