Aurora-B/AIM-1 regulates the dynamic behavior of HP1α at the G2-M transition
Aurora-B/AIM-1 regulates the dynamic behavior of HP1α at the G2-M transition
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DOI：
10.1091/mbc.e05-09-0906
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发表时间：
2006-07-01
影响因子：
3.3
通讯作者：
Terada, Yasuhiko
中科院分区：
文献类型：
--
作者：
Terada, Yasuhiko
异染色质蛋白I（HP 1）在异染色质形成中起重要作用，并在前期细胞中经历大规模的、进行性的异染色质解离。然而，调节HP 1的动态行为的机制知之甚少。在这项研究中，Aurora-B的作用进行了研究，相对于HP 1 α的动态行为。哺乳动物Aurora-B，AIM-1，与HP 1 α共定位于G中的异染色质，Aurora-B/AIM-1的耗尽抑制HP 1 α在G（2）-M转换处从染色体臂上解离。此外，INCENP的缺失导致Aurora-B/AIM-1的异常细胞定位，但它不影响HP 1 α的异染色质靶向。在二元开关假说中提出，组蛋白H3在Ser-10处的磷酸化负调节HP 1 α与相邻的甲基化Lys-9的结合。然而，Aurora-B/AIM-1介导的H3磷酸化诱导了体外HP 1 α染色体结构域的解离，而不是完整蛋白的解离，表明HP 1 α的中心和/或C-末端结构域干扰了H3磷酸化对HP 1 α解离的影响。有趣的是，Lys-9甲基转移酶SUV 39 H1在Aurora-B/AIM 1缺失的细胞中沿着中期染色体臂沿着异常定位在一起。总之，这些结果表明，Aurora-B/AIM-1是必要的调节组蛋白修饰参与有丝分裂过程中的组蛋白H3的N末端的HP 1 α的结合。
Heterochromatin protein I (HP1) plays an important role in heterochromatin formation and undergoes large-scale, progressive dissociation from heterochromatin in prophase cells. However, the mechanisms regulating the dynamic behavior of HP1 are poorly understood. In this study, the role of Aurora-B was investigated with respect to the dynamic behavior of HP1 alpha. Mammalian Aurora-B, AIM-1, colocalizes with HP1 alpha to the heterochromatin in G, Depletion of Aurora-B/AIM-1 inhibited dissociation of HP1 alpha from the chromosome arms at the G(2)-M transition. In addition, depletion of INCENP led to aberrant cellular localization of Aurora-B/AIM-1, but it did not affect heterochromatin targeting of HP1 alpha. It was proposed in the binary switch hypothesis that phosphorylation of histone H3 at Ser-10 negatively regulates the binding of HP1 alpha to the adjacent methylated Lys-9. However, Aurora-B/AIM-1-mediated phosphorylation of H3 induced dissociation of the HP1 alpha chromodomain but not of the intact protein in vitro, indicating that the center and/or C-terminal domain of HP1 alpha interferes with the effect of H3 phosphorylation on HP1 alpha dissociation. Interestingly, Lys-9 methyltransferase SUV39H1 is abnormally localized together along the metaphase chromosome arms in Aurora-B/AIM1-depleted cells. In conclusion, these results showed that Aurora-B/AIM-1 is necessary for regulated histone modifications involved in binding of HP1 alpha by the N terminus of histone H3 during mitosis.