INO80 regulates chromatin accessibility to facilitate suppression of sex-linked gene expression during mouse spermatogenesis

PLoS Genet. 2024 Oct 15;20(10):e1011431. doi: 10.1371/journal.pgen.1011431. eCollection 2024 Oct.

Abstract

The INO80 protein is the main catalytic subunit of the INO80-chromatin remodeling complex, which is critical for DNA repair and transcription regulation in murine spermatocytes. In this study, we explored the role of INO80 in silencing genes on meiotic sex chromosomes in male mice. INO80 immunolocalization at the XY body in pachytene spermatocytes suggested a role for INO80 in the meiotic sex body. Subsequent deletion of Ino80 resulted in high expression of sex-linked genes. Furthermore, the active form of RNA polymerase II at the sex chromosomes of Ino80-null pachytene spermatocytes indicates incomplete inactivation of sex-linked genes. A reduction in the recruitment of initiators of meiotic sex chromosome inhibition (MSCI) argues for INO80-facilitated recruitment of DNA repair factors required for silencing sex-linked genes. This role of INO80 is independent of a common INO80 target, H2A.Z. Instead, in the absence of INO80, a reduction in chromatin accessibility at DNA repair sites occurs on the sex chromosomes. These data suggest a role for INO80 in DNA repair factor localization, thereby facilitating the silencing of sex-linked genes during the onset of pachynema.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Animals
  • Chromatin Assembly and Disassembly / genetics
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Silencing
  • Histones / genetics
  • Histones / metabolism
  • Male
  • Meiosis / genetics
  • Mice
  • Mice, Knockout
  • Pachytene Stage / genetics
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Sex Chromosomes / genetics
  • Spermatocytes* / metabolism
  • Spermatogenesis* / genetics

Substances

  • Chromatin
  • INO80 protein, mouse
  • ATPases Associated with Diverse Cellular Activities
  • DNA-Binding Proteins
  • DNA Helicases
  • RNA Polymerase II
  • Histones