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

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. •Retention of CENP-A underpins centromere inheritance through the female germline•CENP-A persists at high levels >1 year after deposition at mouse oocyte centromeres•CENP-A assembled into chromatin before birth suffices for fertility many months later•CENP-A is a long-lived protein, essential to the function of a totipotent cell To determine the mechanism by which centromeres are inherited through the female germline, Smoak et al. conditionally delete histone H3 variant Cenpa in oocytes in resting primordial follicles. They find that CENP-A nucleosomes assembled before birth suffice for genome transmission to embryos through the fertile lifespan of the mouse.