Methylation of CenH3 arginine 37 regulates kinetochore integrity and chromosome segregation
Methylation of CenH3 arginine 37 regulates kinetochore integrity and chromosome segregation
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DOI：
10.1073/pnas.1120968109
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发表时间：
2012-06-05
影响因子：
11.1
通讯作者：
Ehrenhofer-Murray, Ann E.
中科院分区：
文献类型：
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作者：
Samel, Anke;Cuomo, Alessandro;Ehrenhofer-Murray, Ann E.
真核生物染色体的着丝粒是着丝粒形成和微管附着的标志，对染色体的精确分离至关重要。虽然着丝粒身份是由组蛋白H3变体CenH 3/着丝粒蛋白A（CENP-A）的存在所定义的，但对CenH 3上的表观遗传修饰如何调节动粒组装和着丝粒功能知之甚少。在这里，我们表明，CENP-A从酿酒酵母，被称为Cse 4，是甲基化的精氨酸37（R37），这种甲基化调节着丝粒序列的着丝粒组件的招聘。Cse 4 R37甲基化的缺乏导致缺乏着丝粒结合因子Cbf 1的细胞生长缺陷，并且当与将内部动粒连接到微管结合蛋白的Ctf 19接头复合物的组分中的突变相结合时，导致合成致死。细胞周期阻滞在G2/M期，质粒和染色体分离缺陷。此外，在不存在Cse 4 R37甲基化的情况下，着丝粒处的Mtw 1/MIND（Mtw 1包括Nnf 1-Nsl 1-Dsn 1）和Ctf 19组分的水平降低，但Cse 4本身的水平不降低，从而表明这种修饰调节连接子组分向着丝粒的募集。总之，我们的数据确定了一个独特的调控原则，着丝粒染色质的翻译后修饰的氨基末端的CenH 3。
Centromeres of eukaryotic chromosomes mark the site for kinetochore formation and microtubule attachment and are essential for accurate chromosome segregation. Although centromere identity is defined by the presence of the histone H3 variant CenH3/centromere protein A (CENP-A), little is known about how epigenetic modifications on CenH3 might regulate kinetochore assembly and centromere function. Here we show that CENP-A from Saccharomyces cerevisiae, termed Cse4, is methylated on arginine 37 (R37) and that this methylation regulates the recruitment of kinetochore components to centromeric sequences. The absence of Cse4 R37 methylation caused a growth defect in cells lacking the centromere binding factor Cbf1 and synthetic lethality when combined with mutations in components of the Ctf19 linker complex that connects the inner kinetochore to microtubule-binding proteins. The cells showed a cell-cycle arrest in G2/M phase and defects in plasmid and chromosome segregation. Furthermore, the levels of Mtw1/MIND (Mtw1 including Nnf1-Nsl1-Dsn1) and Ctf19 components at the centromere, but not of Cse4 itself, were reduced in the absence of Cse4 R37 methylation, thus showing that this modification regulates the recruitment of linker components to the centromere. Altogether, our data identify a unique regulatory principle on centromeric chromatin by posttranslational modification of the amino terminus of CenH3.