Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS Genet. 2024 Oct 15;20(10):e1011431. doi: 10.1371/journal.pgen.1011431. eCollection 2024 Oct.
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.
INO80 蛋白是 INO80-染色质重塑复合物的主要催化亚基，该复合物对于小鼠精母细胞中的 DNA 修复和转录调控至关重要。在这项研究中，我们探索了 INO80 在雄性小鼠减数分裂性染色体基因沉默中的作用。在粗线期精母细胞的 XY 体中，INO80 的免疫定位表明 INO80 参与了减数分裂性体的形成。随后，Ino80 的缺失导致了性连锁基因的高表达。此外，在 Ino80 缺失的粗线期精母细胞的性染色体上，RNA 聚合酶 II 的活性形式表明性连锁基因的不完全失活。减数分裂性染色体抑制（MSCI）起始因子的募集减少表明 INO80 有助于募集沉默性连锁基因所需的 DNA 修复因子。INO80 的这种作用不依赖于常见的 INO80 靶标 H2A.Z。相反，在没有 INO80 的情况下，性染色体上的 DNA 修复位点的染色质可及性降低。这些数据表明 INO80 在 DNA 修复因子定位中的作用，从而在粗线期开始时促进了性连锁基因的沉默。
