Two Histone Marks Establish the Inner Centromere and Chromosome Bi-Orientation

Two Histone Marks Establish the Inner Centromere and Chromosome Bi-Orientation
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DOI:
10.1126/science.1194498
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发表时间:
2010-10-08
期刊:
影响因子:
56.9
通讯作者:
Watanabe, Yoshinori
Watanabe, Yoshinori
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yamagishi, Yuya;Honda, Takashi;Watanabe, Yoshinori

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为了在有丝分裂中染色体的正确分配,包括Aurora B和survivin在内的染色体乘客复合体(CPC)必须定位在成对着丝点的中心,即称为内着丝粒的位置。是什么定义了内部着丝粒,以及CPC如何定位到这个位置,这在很大程度上是未知的。在这里,我们发现Haspin介导的组蛋白h3 -苏氨酸3 (H3-pT3)磷酸化与bub1介导的组蛋白2a -丝氨酸121 (H2A-S121)磷酸化协同作用,将CPC靶向到裂变酵母和人类细胞的内着丝粒。H3-pT3促进survivin的核小体结合,而磷酸化的H2A-S121促进shugoshin的结合,shugoshin是着丝体CPC接头。Haspin通过与Pds5结合与粘聚蛋白共定位,而Bub1定位于着丝点。因此,内部着丝粒是由两个组蛋白激酶的交集来定义的。
For proper partitioning of chromosomes in mitosis, the chromosomal passenger complex (CPC) including Aurora B and survivin must be localized at the center of paired kinetochores, at the site called the inner centromere. It is largely unknown what defines the inner centromere and how the CPC is targeted to this site. Here, we show that the phosphorylation of histone H3-threonine 3 (H3-pT3) mediated by Haspin cooperates with Bub1-mediated histone 2A-serine 121 (H2A-S121) phosphorylation in targeting the CPC to the inner centromere in fission yeast and human cells. H3-pT3 promotes nucleosome binding of survivin, whereas phosphorylated H2A-S121 facilitates the binding of shugoshin, the centromeric CPC adaptor. Haspin colocalizes with cohesin by associating with Pds5, whereas Bub1 localizes at kinetochores. Thus, the inner centromere is defined by intersection of two histone kinases.