母体着丝粒蛋白C可恢复哺乳动物受精卵中的着丝粒对称性，以确保染色体正确分离。
Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation.
作者信息
Tower Catherine A, Manske Gabriel, Ferrell Emily L, Anbarci Dilara N, Jorgensen Kelsey, Ma Binbin, Aboelenain Mansour, Ranjan Rajesh, Chakraborty Saikat, Moritz Lindsay, Das Arunika, Boiani Michele, Black Ben E, Chavez Shawn, Marsh Erica E, Shikanov Ariella, Schindler Karen, Chen Xin, Hammoud Saher Sue
机构信息
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Dev Cell. 2025 Sep 24. doi: 10.1016/j.devcel.2025.08.017.
Across metazoan species, the centromere-specific histone variant CENP-A is essential for accurate chromosome segregation, yet its regulation during the mammalian parental-to-zygote transition is poorly understood. To address this, we generated a CENP-A-mScarlet mouse model that revealed sex-specific dynamics: mature sperm retain 10% of the CENP-A levels present in MII oocytes. However, this difference is resolved in zygotes prior to the first mitosis, using maternally inherited cytoplasmic CENP-A. Notably, the increase in CENP-A at paternal centromeres is independent of sensing CENP-A asymmetry or the presence of maternal chromosomes. Instead, CENP-A equalization relies on the asymmetric recruitment of maternal CENP-C to paternal centromeres. Depletion of maternal CENP-A decreases total CENP-A in both pronuclei without disrupting equalization. In contrast, reducing maternal CENP-C or disruption of its dimerization function impairs CENP-A equalization and chromosome segregation. Therefore, maternal CENP-C acts as a key epigenetic regulator that resets centromeric symmetry at fertilization to preserve genome integrity.
在多细胞动物物种中，着丝粒特异性组蛋白变体CENP - A对于准确的染色体分离至关重要，然而其在哺乳动物亲代到合子转变过程中的调控机制却知之甚少。为了解决这个问题，我们构建了一个CENP - A - mScarlet小鼠模型，该模型揭示了性别特异性动态变化：成熟精子保留了MII期卵母细胞中10%的CENP - A水平。然而，这种差异在第一次有丝分裂之前的合子中通过母系遗传的细胞质CENP - A得以解决。值得注意的是，父本着丝粒上CENP - A的增加独立于对CENP - A不对称性的感知或母本染色体的存在。相反，CENP - A的均衡依赖于母本CENP - C向父本着丝粒的不对称募集。母本CENP - A的缺失会降低两个原核中的总CENP - A水平，而不会破坏均衡。相比之下，减少母本CENP - C或破坏其二聚化功能会损害CENP - A的均衡和染色体分离。因此，母本CENP - C作为关键的表观遗传调节因子，在受精时重置着丝粒对称性以维持基因组完整性。
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