INO80 regulates chromatin accessibility to facilitate meiotic sex chromosome inactivation

Abstract

AbstractThe 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. Robust INO80 immunolocalization at the XY body in pachytene spermatocytes suggested a role for INO80 in the meiotic sex body. Subsequent deletion ofIno80resulted in high expression of sex-linked genes. Furthermore, the active form of RNA polymerase II at the sex body ofIno80-null pachytene spermatocytes indicates incomplete meiotic sex chromosome inactivation (MSCI). A reduction in the recruitment of MSCI initiators argues for INO80-facilitated recruitment of DNA repair factors required for MSCI initiation. 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 unique role for INO80 in DNA repair factor localization, thereby facilitating the silencing of sex-linked genes during the onset of pachynema.