Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1

Nat Commun. 2015 Dec 11:6:10026. doi: 10.1038/ncomms10026.

Abstract

Little is known how lincRNAs are involved in skeletal myogenesis. Here we describe the discovery of Linc-YY1 from the promoter of the transcription factor (TF) Yin Yang 1 (YY1) gene. We demonstrate that Linc-YY1 is dynamically regulated during myogenesis in vitro and in vivo. Gain or loss of function of Linc-YY1 in C2C12 myoblasts or muscle satellite cells alters myogenic differentiation and in injured muscles has an impact on the course of regeneration. Linc-YY1 interacts with YY1 through its middle domain, to evict YY1/Polycomb repressive complex (PRC2) from target promoters, thus activating the gene expression in trans. In addition, Linc-YY1 also regulates PRC2-independent function of YY1. Finally, we identify a human Linc-YY1 orthologue with conserved function and show that many human and mouse TF genes are associated with lincRNAs that may modulate their activity. Altogether, we show that Linc-YY1 regulates skeletal myogenesis and uncover a previously unappreciated mechanism of gene regulation by lincRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Embryo, Mammalian
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Mice
  • Mice, Inbred mdx
  • Muscle Development / physiology*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Regeneration / physiology
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism*

Substances

  • RNA, Long Noncoding
  • YY1 Transcription Factor
  • Yy1 protein, mouse