ZSCAN4 functions as a safeguard to maintain centromere integrity during oocyte meiosis.

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.