Centromeres are defined epigenetically by the histone H3 variant CENP-A. The propagation cycle by which pre-existing CENP-A nucleosomes serve as templates for nascent assembly predicts the epigenetic memory of weakened centromeres. Using a mouse model with reduced levels of CENP-A nucleosomes, we find that an embryonic plastic phase precedes epigenetic memory through development. During this phase, nascent CENP-A nucleosome assembly depends on the maternal Cenpa genotype rather than the pre-existing template. Weakened centromeres are thus limited to a single generation, and parental epigenetic differences are eliminated by equal assembly on maternal and paternal centromeres. These differences persist, however, when the underlying DNA of parental centromeres differs in repeat abundance, as assembly during the plastic phase also depends on sufficient repetitive centromere DNA. With contributions of centromere DNA and the Cenpa maternal effect, we propose that centromere inheritance naturally minimizes fitness costs associated with weakened centromeres or epigenetic differences between parents.

着丝粒由组蛋白 H3 变体 CENP-A 在表观遗传学上定义。预先存在的 CENP-A 核小体作为新生组装模板的传播周期预测了弱化着丝粒的表观遗传记忆。使用 CENP-A 核小体水平降低的小鼠模型，我们发现胚胎可塑性阶段先于发育的表观遗传记忆。在此阶段，新生的 CENP-A 核小体组装依赖于母体Cenpa基因型而不是预先存在的模板。因此，弱化的着丝粒仅限于单代，并且父母的表观遗传差异通过母本和父本着丝粒的平等组装而消除。然而，当亲本着丝粒的基础 DNA 的重复丰度不同时，这些差异仍然存在，因为塑性阶段的组装也取决于足够的重复着丝粒 DNA。由于着丝粒 DNA 的贡献和Cenpa母体效应，我们提出着丝粒遗传自然地最小化了与着丝粒减弱或父母之间的表观遗传差异相关的适应度成本。