Choi Da Yi, Leem Jiyeon, Lee Crystal, Oh Jeong Su
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Korea.
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Korea.
Genome Biol. 2025 Jul 15;26(1):204. doi: 10.1186/s13059-025-03687-3.
Centromeres play a vital role in ensuring accurate chromosome segregation during meiosis by serving as the foundation for kinetochore assembly and microtubule attachment. In oocytes, maintaining centromere integrity is particularly critical due to the extended arrest period prior to meiotic resumption. However, the molecular safeguards that preserve centromere structure and function throughout oocyte maturation remain poorly understood.
Here, we identify ZSCAN4 as an essential regulator of centromere integrity during mouse oocyte meiosis. ZSCAN4 depletion leads to a marked reduction in key centromeric and kinetochore proteins, including CENP-A, accompanied by aberrant centromere stretching under spindle tension. Mechanistically, ZSCAN4 promotes pericentromeric H3K9me3 enrichment, facilitating proper chromatin compaction and chromosome alignment. Moreover, ZSCAN4 contributes to genomic stability by mediating the chromosomal recruitment of the CIP2A complex in response to DNA damage during meiotic progression.
These findings establish ZSCAN4 as a critical factor in preserving centromere structure and function during oocyte meiosis, with potential implications for female reproductive health and developmental competence.
着丝粒在减数分裂过程中通过作为动粒组装和微管附着的基础，在确保染色体准确分离方面发挥着至关重要的作用。在卵母细胞中，由于减数分裂恢复前的延长停滞期，维持着丝粒完整性尤为关键。然而，在整个卵母细胞成熟过程中保护着丝粒结构和功能的分子保障机制仍知之甚少。
在这里，我们确定ZSCAN4是小鼠卵母细胞减数分裂过程中着丝粒完整性的关键调节因子。ZSCAN4的缺失导致包括CENP-A在内的关键着丝粒和动粒蛋白显著减少，同时在纺锤体张力下着丝粒出现异常拉伸。从机制上讲，ZSCAN4促进着丝粒周围H3K9me3富集，促进适当的染色质压缩和染色体排列。此外，ZSCAN4通过在减数分裂进程中响应DNA损伤介导CIP2A复合物的染色体募集，从而有助于基因组稳定性。
这些发现确立了ZSCAN4是卵母细胞减数分裂过程中维持着丝粒结构和功能的关键因素，对女性生殖健康和发育能力具有潜在影响。
