Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13598-0
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Funding
- General Research Fund (GRF) from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region [14133016, 14106117, 14100018, 14115319, 14102315, 14116918, 14120619]
- National Natural Science Foundation of China (NSFC) [31871304]
- NSFC/RGC Joint Research Scheme [N_CUHK413/18]
- Focused Innovations Scheme: Scheme B [1907307]
- RGC Collaborative Research Fund (CRF) from RGC [C6015-14G]
- Hong Kong Epigenomics Project (EpiHK) Fund
- Youth Innovation Promotion Association of the Chinese Academy of Sciences [2015294]
- Natural Science Foundation of Guangdong Province [2018B030306042]
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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.
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