Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential.
Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential.
复制标题
静止细胞主动补充 CENP-A 核小体，以维持着丝粒身份和增殖潜力。
DOI：
10.1016/j.devcel.2019.07.016
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发表时间：
2019
影响因子：
11.8
通讯作者：
Cheeseman,IainM
中科院分区：
文献类型：
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作者：
Swartz,SZachary;McKay,LilianaS;Su,Kuan-Chung;Bury,Leah;Padeganeh,Abbas;Maddox,PaulS;Knouse,KristinA;Cheeseman,IainM
着丝粒是由与组蛋白h3变异着丝粒蛋白a （CENP-A）相关的序列无关机制指定的，因此为表观遗传提供了一个强大的模型。流行的模型表明，CENP-A核小体的高内在稳定性无限期地维持着丝粒的同一性。在这里，我们证明了CENP-A在着丝粒中并不稳定，而是逐渐和持续地掺入静止细胞，包括g0阻滞的组织培养细胞和前期i阻滞的卵母细胞。静止的CENP-A结合涉及典型的CENP-A沉积机制，但与细胞周期依赖的沉积有不同的要求。我们证明了Plk1是G1期CENP-A沉积所必需的，而转录促进了静止卵母细胞中CENP-A的掺入。在休眠期间阻止CENP-A沉积会导致显著降低CENP-A水平，并扰乱细胞分裂恢复后的染色体分离。与静止细胞相比，终分化细胞不能维持CENP-A水平。我们的研究表明，静止细胞积极地维持着丝粒的同一性，为增殖潜力提供了一个指标。
Centromeres provide a robust model for epigenetic inheritance as they are specified by sequence-independent mechanisms involving the histone H3-variant centromere protein A (CENP-A). Prevailing models indicate that the high intrinsic stability of CENP-A nucleosomes maintains centromere identity indefinitely. Here, we demonstrate that CENP-A is not stable at centromeres but is instead gradually and continuously incorporated in quiescent cells including G0-arrested tissue culture cells and prophase I-arrested oocytes. Quiescent CENP-A incorporation involves the canonical CENP-A deposition machinery but displays distinct requirements from cell cycle-dependent deposition. We demonstrate that Plk1 is required specifically for G1 CENP-A deposition, whereas transcription promotes CENP-A incorporation in quiescent oocytes. Preventing CENP-A deposition during quiescence results in significantly reduced CENP-A levels and perturbs chromosome segregation following the resumption of cell division. In contrast to quiescent cells, terminally differentiated cells fail to maintain CENP-A levels. Our work reveals that quiescent cells actively maintain centromere identity providing an indicator of proliferative potential.