Breaking the HAC Barrier: histone H3K9 acetyl/methyl balance regulates CENP-A assembly.
Breaking the HAC Barrier: histone H3K9 acetyl/methyl balance regulates CENP-A assembly.
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DOI：
10.1038/emboj.2012.82
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发表时间：
2012-05-16
期刊：
影响因子：
11.4
通讯作者：
Masumoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Ohzeki, Jun-ichirou;Bergmann, Jan H.;Kouprina, Natalay;Noskov, Vladimir N.;Nakano, Megumi;Kimura, Hiroshi;Earnshaw, William C.;Larionov, Vladimir;Masumoto, Hiroshi
动粒负责染色体的精确分离。然而，动粒组装和维持的机制仍不清楚。在这里，我们报告，从头CENP-A大会和着丝粒形成人类着丝粒α DNA阵列的组蛋白H3 K9乙酰基/甲基平衡的调节。将组蛋白乙酰转移酶（HAT）拴系到α DNA阵列打破了从头稳定CENP-A组装的细胞类型特异性屏障，并诱导其他动粒蛋白在异位α位点组装。CENP-A沉积因子hMis 18 α或HJURP的束缚也获得了类似的结果。HAT系链绕过了对hMis 18 α的需要，但HJURP仍然是从头动粒组装所必需的。相比之下，H3 K9三甲基化酶（Suv 39 h1）拴系到阵列后的H3 K9甲基化阻止了从头CENP-A组装和动粒形成。通过这种机制从头组装的CENP-A阵列可以形成在人类细胞中无限繁殖的人类人工染色体（HAC）。
The kinetochore is responsible for accurate chromosome segregation. However, the mechanism by which kinetochores assemble and are maintained remains unclear. Here we report that de novo CENP-A assembly and kinetochore formation on human centromeric alphoid DNA arrays is regulated by a histone H3K9 acetyl/methyl balance. Tethering of histone acetyltransferases (HATs) to alphoid DNA arrays breaks a cell type-specific barrier for de novo stable CENP-A assembly and induces assembly of other kinetochore proteins at the ectopic alphoid site. Similar results are obtained following tethering of CENP-A deposition factors hMis18α or HJURP. HAT tethering bypasses the need for hMis18α, but HJURP is still required for de novo kinetochore assembly. In contrast, H3K9 methylation following tethering of H3K9 tri-methylase (Suv39h1) to the array prevents de novo CENP-A assembly and kinetochore formation. CENP-A arrays assembled de novo by this mechanism can form human artificial chromosomes (HACs) that are propagated indefinitely in human cells.
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