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

Cell Res. 2015 Mar;25(3):335-50. doi: 10.1038/cr.2015.21. Epub 2015 Feb 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation / genetics
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development / genetics*
  • Muscle Development / physiology
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / growth & development
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myoblasts / cytology
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Primary Cell Culture
  • Promoter Regions, Genetic / genetics
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering
  • Regeneration / genetics
  • Regeneration / physiology
  • Transcription Factors

Substances

  • DNMT3A protein, human
  • Dnmt3a protein, mouse
  • Dppa2 protein, mouse
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Transcription Factors
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Dnmt1 protein, mouse