Centromeres are built on repetitive DNA sequences (CenDNA) and a specific chromatin enriched with the histone H3 variant CENP‐A, the epigenetic mark that identifies centromere position. Here, we interrogate the importance of CenDNA in centromere specification by developing a system to rapidly remove and reactivate CENP‐A (CENP‐A^OFF/ON). Using this system, we define the temporal cascade of events necessary to maintain centromere position. We unveil that CENP‐B bound to CenDNA provides memory for maintenance on human centromeres by promoting de novo CENP‐A deposition. Indeed, lack of CENP‐B favors neocentromere formation under selective pressure. Occasionally, CENP‐B triggers centromere re‐activation initiated by CENP‐C, but not CENP‐A, recruitment at both ectopic and native centromeres. This is then sufficient to initiate the CENP‐A‐based epigenetic loop. Finally, we identify a population of CENP‐A‐negative, CENP‐B/C‐positive resting CD4⁺ T cells capable to re‐express and reassembles CENP‐A upon cell cycle entry, demonstrating the physiological importance of the genetic memory.

中文翻译：

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遗传记忆启动了保持着丝粒位置所必需的表观遗传环。

着丝粒建立在重复 DNA 序列 (CenDNA) 和富含组蛋白 H3 变体 CENP-A 的特定染色质上，CENP-A 是识别着丝粒位置的表观遗传标记。^{在这里，我们通过开发一个快速去除和重新激活 CENP-A (CENP-A OFF/ON} )的系统来询问 CenDNA 在着丝粒规范中的重要性。使用这个系统，我们定义了维持着丝粒位置所必需的事件的时间级联。我们揭示了与 CenDNA 结合的 CENP-B 通过促进从头开始为人类着丝粒的维持提供记忆CENP-A 沉积。事实上，缺乏 CENP-B 有利于在选择性压力下形成新着丝粒。偶尔，CENP-B 会触发由 CENP-C 而不是 CENP-A 启动的着丝粒重新激活，在异位和天然着丝粒处募集。这足以启动基于 CENP-A 的表观遗传循环。最后，我们确定了一组 CENP-A 阴性、CENP-B/C 阳性静息 CD4 ⁺ T 细胞能够在进入细胞周期时重新表达和重新组装 CENP-A，证明了遗传记忆的生理重要性。