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

Yu Zhao, Jiajian Zhou, Liangqiang He, Yuying Li, Jie Yuan, Kun Sun, Xiaona Chen, Xichen Bao, Miguel A. Esteban, Hao Sun () and Huating Wang ()
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Yu Zhao: The Chinese University of Hong Kong
Jiajian Zhou: The Chinese University of Hong Kong
Liangqiang He: The Chinese University of Hong Kong
Yuying Li: The Chinese University of Hong Kong
Jie Yuan: The Chinese University of Hong Kong
Kun Sun: The Chinese University of Hong Kong
Xiaona Chen: The Chinese University of Hong Kong
Xichen Bao: Chinese Academy of Sciences
Miguel A. Esteban: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Hao Sun: The Chinese University of Hong Kong
Huating Wang: The Chinese University of Hong Kong

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13598-0

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