Volume 25, No 3, Mar 2015

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 25 Issue 3, March 2015: 335-350

ORIGINAL ARTICLES

LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration

Lijun Wang¹, Yu Zhao², Xichen Bao³, Xihua Zhu³, Yvonne Ka-yin Kwok², Kun Sun⁴, Xiaona Chen², Yongheng Huang⁵, Ralf Jauch⁵, Miguel A Esteban³, Hao Sun⁴ and Huating Wang¹

¹Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
²Department of Obstetrics and Gynaecology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
³Laboratory of Chromatin and Human Disease, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
⁴Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
⁵Genome Regulation Laboratory, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China Correspondence: Huating Wang, Tel: +(852) 3763-6047; Fax: +(852) 2636-0008 E-mail: huating.wang@cuhk.edu.hk; Hao Sun,(haosun@cuhk.edu.hk)

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.

10.1038/cr.2015.21

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