MyoD induced enhancer RNA interacts with hnRNPL to activate target gene transcription during myogenic differentiation

Nat Commun. 2019 Dec 19;10(1):5787. doi: 10.1038/s41467-019-13598-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Enhancer Elements, Genetic / genetics*
  • Gene Expression Regulation, Developmental*
  • Heterogeneous-Nuclear Ribonucleoprotein L / genetics*
  • Male
  • Mice
  • Muscle Development / genetics*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / growth & development
  • MyoD Protein / metabolism*
  • Myoblasts / physiology
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Transcription, Genetic


  • Heterogeneous-Nuclear Ribonucleoprotein L
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • RNA, Messenger