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

• DOI: 10.1038/cr.2015.21
• Publication Date: 2015-02-17T11:33:32Z
• Authors: Lijun Wang; Yu Zhao; Xichen Bao; Xihua Zhu; Yvonne Ka-yin Kwok; Kun Sun; Xiaona Chen; Yongheng Huang; Ralf Jauch; Miguel A Esteban; Hao Sun; Huating Wang
• Keywords: DNA (Cytosine-5-)-Methyltransferase 1; 0301 basic medicine; Primary Cell Culture; Muscle Development; Cell Line; DNA Methyltransferase 3A; Myoblasts; Mice; 03 medical and health sciences; Dum; Animals; Regeneration; DNA (Cytosine-5-)-Methyltransferases; RNA, Small Interfering; Muscle, Skeletal; Promoter Regions, Genetic; MyoD Protein; DNA methylation; Nuclear Proteins; Cell Differentiation; DNA Methylation; Dppa2; LncRNA; Mice, Inbred C57BL; RNA Interference; RNA, Long Noncoding; myogenesis

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.