H2A.Z is a H2A-type histone variant essential for many aspects of cell biology, ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues, H2A.Z.1 and H2A.Z.2, that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV, respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here, we have investigated the distinct roles of the two paralogues in cell cycle regulation and unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division. Our findings show that H2A.Z.1 regulates the expression of cell cycle genes such as Myc and Ki-67 and its depletion leads to a G1 arrest and cellular senescence. On the contrary, H2A.Z.2, in a transcription-independent manner, is essential for centromere integrity and sister chromatid cohesion regulation, thus playing a key role in chromosome segregation.

中文翻译：

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H2A.Z.1 和 H2A.Z.2 在染色体分离和细胞周期进程中的非冗余功能

H2A.Z 是一种 H2A 型组蛋白变体，对于细胞生物学的许多方面（从基因表达到基因组稳定性）都是必不可少的。H2A.Z 从后口动物进化成两个旁系同源物 H2A.Z.1 和 H2A.Z.2，它们仅相差三个氨基酸，并由不同的基因（H2AFZ和H2AFV）编码， 分别）。尽管这种组蛋白变体在发育和细胞稳态中很重要，但对哺乳动物中每个旁系同源物的个体功能知之甚少。在这里，我们研究了两种旁系同源物在细胞周期调节中的不同作用，并揭示了 H2A.Z.1 和 H2A.Z.2 在细胞分裂中的非冗余功能。我们的研究结果表明，H2A.Z.1 调节细胞周期基因（如 Myc 和 Ki-67）的表达，其消耗导致 G1 期停滞和细胞衰老。相反，H2A.Z.2 以不依赖转录的方式，对着丝粒完整性和姐妹染色单体内聚力调节至关重要，因此在染色体分离中起关键作用。