The mitotic kinase Aurora B regulates the condensation of chromatin into chromosomes by phosphorylating chromatin proteins during early mitosis, whereas the phosphatase PP1γ performs the opposite function. The roles of Aurora B and PP1γ must be tightly coordinated to maintain chromosomes at a high phosphorylation state, but the precise mechanisms regulating their function remain largely unclear. Here, mainly through immunofluorescence microscopy and co-immunoprecipitation assays, we find that dissociation of PP1γ from chromosomes is essential for maintaining chromosome phosphorylation. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ–Repo-Man interactions on chromatin. Overexpression of Repo-Man mutants that cannot be phosphorylated or inhibition of Aurora B kinase activity resulted in the retention of PP1γ on chromatin and prolonged the chromatin condensation process; a similar outcome was caused by the ectopic targeting of PP1γ to chromatin. Together, our findings reveal a novel regulation mechanism of chromatin condensation in which Aurora B counteracts PP1γ activity by releasing PP1γ from Repo-Man and may have important implications for understanding the regulations of dynamic structural changes of the chromosomes in mitosis.

中文翻译：

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Aurora B 调节 PP1γ-Repo-Man 相互作用以维持染色体凝聚状态。

有丝分裂激酶 Aurora B 通过在早期有丝分裂期间磷酸化染色质蛋白来调节染色质凝聚成染色体，而磷酸酶 PP1γ 则执行相反的功能。Aurora B 和 PP1γ 的作用必须紧密协调以将染色体维持在高磷酸化状态，但调节其功能的精确机制仍不清楚。在这里，主要通过免疫荧光显微镜和免疫共沉淀分析，我们发现 PP1γ 从染色体上的解离对于维持染色体磷酸化是必不可少的。我们发现在没有 Aurora B 活性的情况下，PP1γ 被其调节亚基 Repo-Man 募集到有丝分裂染色体，并且 Aurora B 通过磷酸化和破坏染色质上的 PP1γ-Repo-Man 相互作用来调节 PP1γ 的解离。不能磷酸化或抑制 Aurora B 激酶活性的 Repo-Man 突变体的过度表达导致 PP1γ 保留在染色质上并延长染色质凝聚过程；PP1γ 异位靶向染色质导致了类似的结果。总之，我们的研究结果揭示了一种新的染色质凝聚调控机制，其中 Aurora B 通过从 Repo-Man 释放 PP1γ 来抵消 PP1γ 的活性，并且可能对理解有丝分裂中染色体动态结构变化的调控具有重要意义。