Chromosome segregation during cell division is driven by mitotic spindle attachment to the centromere region on each chromosome. Centromeres form a protein scaffold defined by chromatin featuring CENP-A, a conserved histone H3 variant, in a manner largely independent of local DNA cis elements. CENP-A nucleosomes fulfill two essential criteria to epigenetically identify the centromere. They undergo self-templated duplication to reestablish centromeric chromatin following DNA replication. More importantly, CENP-A incorporated into centromeric chromatin is stably transmitted through consecutive cell division cycles. CENP-A nucleosomes have unique structural properties and binding partners that potentially explain their long lifetime in vivo. However, rather than a static building block, centromeric chromatin is dynamically regulated throughout the cell cycle, indicating that CENP-A stability is also controlled by external factors. We discuss recent insights and identify the outstanding questions on how dynamic control of the long-term stability of CENP-A ensures epigenetic centromere inheritance.

中文翻译：

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CENP-A染色质的稳定遗传：内在力量与动态控制


细胞分裂过程中的染色体分离是由有丝分裂纺锤体附着在每条染色体上的着丝粒区域驱动的。着丝粒形成由染色质定义的蛋白质支架，其特征为 CENP-A（一种保守的组蛋白 H3 变体），其方式很大程度上独立于局部 DNA 顺式元件。 CENP-A 核小体满足表观遗传学识别着丝粒的两个基本标准。它们进行自我模板复制，以在 DNA 复制后重建着丝粒染色质。更重要的是，掺入着丝粒染色质的CENP-A通过连续的细胞分裂周期稳定传递。 CENP-A 核小体具有独特的结构特性和结合伴侣，这可能解释了它们在体内的长寿命。然而，着丝粒染色质不是静态的构建块，而是在整个细胞周期中动态调节，这表明 CENP-A 的稳定性也受到外部因素的控制。我们讨论了最新的见解，并确定了有关 CENP-A 长期稳定性的动态控制如何确保表观遗传着丝粒遗传的突出问题。