Linc-MYH configures INO80 to regulate muscle stem cell numbers and skeletal muscle hypertrophy

EMBO J. 2020 Nov 16;39(22):e105098. doi: 10.15252/embj.2020105098. Epub 2020 Sep 22.

Abstract

Chromatin remodeling complexes have functions in transcriptional regulation and chromosome maintenance, but it is mostly unknown how the function of these normally ubiquitous complexes is specified in the cellular context. Here, we describe that the evolutionary conserved long non-coding RNA linc-MYH regulates the composition of the INO80 chromatin remodeler complex in muscle stem cells and prevents interaction with WDR5 and the transcription factor YY1. Linc-MYH acts as a selective molecular switch in trans that governs the pro-proliferative function of the ubiquitous INO80 complex but does not affect its role in maintaining genomic stability. The molecular switch is essential for restricting generation of quiescent MuSCs and proliferation of myoblasts in homeostasis and regeneration. Since linc-MYH is expressed in proliferating myoblasts but not in quiescent MuSCs, we reason that the extent of myoblast proliferation has decisive effects on the size of the quiescent MuSC pool.

Keywords: Chromatin remodeler; lincRNA; muscle stem cell proliferation; non-coding RNA function; satellite cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Animals
  • Cell Proliferation
  • Chromatin
  • DNA Glycosylases / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epigenomics
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hypertrophy / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Untranslated
  • Regeneration / physiology
  • Transcriptome
  • YY1 Transcription Factor / genetics

Substances

  • Chromatin
  • DNA-Binding Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • YY1 Transcription Factor
  • Yy1 protein, mouse
  • DNA Glycosylases
  • mutY adenine glycosylase
  • ATPases Associated with Diverse Cellular Activities
  • INO80 protein, human
  • INO80 protein, mouse