Abstract
Emerging studies document the roles of long non-coding RNAs (LncRNAs) in regulating gene expression at chromatin level but relatively less is known how they regulate DNA methylation. Here we identify an lncRNA, Dum (developmental pluripotency-associated 2 (Dppa2) Upstream binding Muscle lncRNA) in skeletal myoblast cells. The expression of Dum is dynamically regulated during myogenesis in vitro and in vivo. It is also transcriptionally induced by MyoD binding upon myoblast differentiation. Functional analyses show that it promotes myoblast differentiation and damage-induced muscle regeneration. Mechanistically, Dum was found to silence its neighboring gene, Dppa2, in cis through recruiting Dnmt1, Dnmt3a and Dnmt3b. Furthermore, intrachromosomal looping between Dum locus and Dppa2 promoter is necessary for Dum/Dppa2 interaction. Collectively, we have identified a novel lncRNA that interacts with Dnmts to regulate myogenesis.
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Acknowledgements
We thank Dr Xiaoxing Li for helping bisulfate genomic specific sequencing study. We thank Dr Prasanth KV and Qinyu Hao for their kind help and discussion on FISH experiment. The work described in this paper was substantially supported by General Research Funds (GRF) from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (476310 and 476113 to HW and 473713 to HS), the 973 program of Ministry of Science and Technology of China (2014CB964700 and 2011CB965201), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020106).
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( Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Figure S1 (download PDF )
Dum is a long non-coding RNA. (PDF 358 kb)
Supplementary information, Figure S2 (download PDF )
Knock-down of Dum delayed C2C12 differentiation but over-expression showed no effect. (PDF 62 kb)
Supplementary information, Figure S3 (download PDF )
The neighboring genes of Dum. (PDF 151 kb)
Supplementary information, Figure S4 (download PDF )
Dum binds to Dppa2 promoter. (PDF 194 kb)
Supplementary information, Table S1 (download PDF )
Oligos/Primers used in the study. (PDF 28 kb)
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Wang, L., Zhao, Y., Bao, X. et al. LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration. Cell Res 25, 335–350 (2015). https://doi.org/10.1038/cr.2015.21
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DOI: https://doi.org/10.1038/cr.2015.21
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