Long-Term Retention of CENP-A Nucleosomes in Mammalian Oocytes Underpins Transgenerational Inheritance of Centromere Identity

哺乳动物卵母细胞中CENP-A核小体的长期保留是着丝粒身份跨代遗传的基础

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Abstract

Centromeres control genetic inheritance by directing chromosome segregation but are not genetically encoded themselves. Rather, centromeres are defined by nucleosomes containing CENP-A, a histone H3 variant [1]. In cycling somatic cells, centromere identity is maintained by an established cell-cycle-coupled CENP-A chromatin assembly pathway, but how centromeres are inherited through the mammalian female germline is unclear because of the long (months to decades) prophase I arrest. Here we show that mouse oocytes retain the pool of CENP-A nucleosomes assembled before birth, and that this pool is sufficient for centromere function, fertility, and genome transmission to embryos. Indeed, oocytes lack any measurable CENP-A nucleosome assembly through the entire fertile lifespan of the female (>1 year). Thus, the remarkable stability of CENP-A nucleosomes confers transgenerational centromere identity in mammals.

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