Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression.

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 addressed the question of identifying if the two paralogues have specific roles in cell cycle regulation. Using a specific siRNA approach for each paralogue in human cells, we have unveiled non-redundant roles for H2A.Z.1 and H2A.Z.2 in cell division where H2A.Z.1 regulates the expression of important cell cycle genes (including Myc and Ki-67) whereas H2A.Z.2 is essential for centromere integrity and function thus playing a key role in chromosome segregation.

H2A.Z是一种H2A型组蛋白变体（histone variant），在从基因表达到基因组稳定性的诸多细胞生物学过程中发挥不可或缺的作用。在后口动物（deuterostomes）中，H2A.Z演化出两种旁系同源物（paralogues）H2A.Z.1与H2A.Z.2，二者仅在3个氨基酸位点存在差异，分别由H2AFZ与H2AFV基因编码。尽管该组蛋白变体在发育与细胞稳态中具有重要意义，但目前学界对哺乳动物中这两种旁系同源物的各自功能仍知之甚少。本研究旨在探究这两种旁系同源物在细胞周期调控中是否存在特异性功能。我们通过在人类细胞中针对每种旁系同源物的特异性小干扰RNA（siRNA）技术，揭示了H2A.Z.1与H2A.Z.2在细胞分裂过程中存在非冗余功能：H2A.Z.1可调控包括Myc、Ki-67在内的关键细胞周期基因的表达，而H2A.Z.2对着丝粒的完整性与功能至关重要，因此在染色体分离过程中发挥核心作用。