Epigenetic centromere identity is precisely maintained through DNA replication but is uniquely specified among human cells.
Epigenetic centromere identity is precisely maintained through DNA replication but is uniquely specified among human cells.
复制标题
DOI：
10.26508/lsa.202201807
复制
发表时间：
2023-03
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
人细胞系之间CENP-A富集位置和动粒募集位置的可塑性伴随着在整个细胞周期中精确的CENP-A维持，以保持人细胞中独特的表观遗传着丝粒身份。着丝粒身份是由组蛋白变体CENP-A的存在在表观遗传学上定义和维持的。着丝粒CENP-A的位置是如何通过DNA复制来指定和精确维持的还不完全清楚。最近公布的端粒到端粒（T2 T）基因组组装包含第一个完整的人类着丝粒序列提供了一个新的资源，检查CENP-A的位置。将相同细胞系的克隆中的CENP-A位置映射到T2 T组装体，鉴定了多次细胞分裂后高度相似的CENP-A位置。相比之下，着丝粒CENP-A表观等位基因在不同人细胞系的几个着丝粒处是明显的，表明CENP-A富集的位置和动粒募集的位点在人细胞中不同。在整个细胞周期中，沉积在G1期的CENP-A分子通过DNA复制保持在其精确位置。因此，尽管CENP-A在DNA复制期间被稀释，但CENP-A被精确地重新加载到子着丝粒内的相同序列上，从而在人类细胞中保持独特的着丝粒同一性。
Plasticity in the position of CENP-A enrichment and location of kinetochore recruitment between human cell lines is accompanied by precise CENP-A maintenance across the cell cycle to preserve unique epigenetic centromere identities among human cells. Centromere identity is defined and maintained epigenetically by the presence of the histone variant CENP-A. How centromeric CENP-A position is specified and precisely maintained through DNA replication is not fully understood. The recently released Telomere-to-Telomere (T2T) genome assembly containing the first complete human centromere sequences provides a new resource for examining CENP-A position. Mapping CENP-A position in clones of the same cell line to the T2T assembly identified highly similar CENP-A position after multiple cell divisions. In contrast, centromeric CENP-A epialleles were evident at several centromeres of different human cell lines, demonstrating the location of CENP-A enrichment and the site of kinetochore recruitment vary among human cells. Across the cell cycle, CENP-A molecules deposited in G1 phase are maintained in their precise position through DNA replication. Thus, despite CENP-A dilution during DNA replication, CENP-A is precisely reloaded onto the same sequences within the daughter centromeres, maintaining unique centromere identity among human cells.