Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres
Mis16 and Mis18 are required for CENP-A loading and histone deacetylation at centromeres
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DOI：
10.1016/j.cell.2004.09.002
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发表时间：
2004-09-17
期刊：
影响因子：
64.5
通讯作者：
Yanagida, M
中科院分区：
文献类型：
--
作者：
Hayashi, T;Fujita, Y;Yanagida, M
着丝粒含有特殊的染色质，包括着丝粒特异性组蛋白H3变体spCENP-A/Cnp 1。在这里，我们报告的五个裂殖酵母着丝粒蛋白，Mis 14 -18的鉴定。Mis 14独立于CENP-A被招募到着丝粒，相反，CENP-A不需要Mis 14与着丝粒相关联。相比之下，Mis 15、Mis 16（与人RbAp 48和RbAp 46高度相似）、Mis 17和Mis 18都是CENP-A募集途径的一部分。Mis 15和Mis 17形成了一个进化上保守的复合体，其中也包括Mis 6。Mis 16和Mis 18形成一个复合体，并保持组蛋白的脱乙酰化状态，特别是在中央核心的着丝粒。Mis 16和Mis 18是动粒组装的最上游因子，因为它们可以分别与除mis 18和mis 16之外的所有动粒突变体中的动粒相关联。在人类细胞中的RNAi敲低显示Mis 16功能是保守的，因为RbAp 48和RbAp 46都是人类CENP-A定位所需的。
Centromeres contain specialized chromatin that includes the centromere-specific histone H3 variant, spCENP-A/Cnp1. Here we report identification of five fission yeast centromere proteins, Mis14-18. Mis14 is recruited to kinetochores independently of CENP-A, and, conversely, CENP-A does not require Mis14 to associate with centromeres. In contrast, Mis15, Mis16 (strong similarity with human RbAp48 and RbAp46), Mis17, and Mis18 are all part of the CENP-A recruitment pathway. Mis15 and Mis17form an evolutionarily conserved complex that also includes Mis6. Mis16 and Mis18 form a complex and maintain the deacetylated state of histones specifically in the central core of centromeres. Mis16 and Mis18 are the most upstream factors in kinetochore assembly as they can associate with kinetochores in all kinetochore mutants except for mis18 and mis16, respectively. RNAi knockdown in human cells shows that Mis16 function is conserved as RbAp48 and RbAp46 are both required for localization of human CENP-A.