KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation.
KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation.
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DOI：
10.1016/j.devcel.2016.05.006
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发表时间：
2016-06-06
影响因子：
11.8
通讯作者：
Masumoto H
中科院分区：
文献类型：
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作者：
Ohzeki J;Shono N;Otake K;Martins NM;Kugou K;Kimura H;Nagase T;Larionov V;Earnshaw WC;Masumoto H
含有组蛋白 H3 变体 CENP-A 的着丝粒染色质是准确染色体分离所必需的，作为着丝粒组装的基础。人类着丝粒染色质组装在长 α-卫星（α-卫星）DNA 阵列的一部分上，其两侧是中心周异染色质。异染色质扩散到邻近染色质并抑制基因表达，并且可以拮抗着丝粒功能或 CENP-A 组装。在这里，我们证明了 CENP-A 组装因子 M18BP1 和乙酰转移酶 KAT7/HBO1/MYST2 之间的相互作用。在 HeLa 细胞中敲除 KAT7 会减少着丝粒 CENP-A 的组装。敲除细胞中的有丝分裂染色体错位和微核形成增加，并且当组蛋白 H3-K9 三甲基化酶 Suv39h1 过量产生时增强。将 KAT7 束缚到异位 alphoid DNA 整合位点消除了异染色 H3K9me3 修饰，并足以刺激新的 CENP-A 或组蛋白 H3.3 组装。因此，与 Mis18 复合物结合的含有 KAT7 的乙酰转移酶提供了对 alphaloid DNA 进行组蛋白周转/交换活性的能力，并防止 Suv39h1 介导的异染色质侵入着丝粒。组蛋白乙酰转移酶 KAT7 正向调节着丝粒 CENP-A 组装 人 Mis18 复合体是 KAT7 和 HJURP 组装的支架，CENP-A 伴侣 KAT7 或 RSF1 刺激 alphoid DNA 上的组蛋白周转/交换 KAT7 拮抗 H3K9-三甲基酶 Suv39h1 介导的着丝粒失活 人着丝粒含有组蛋白 H3 变体 CENP-A，并且是两侧为中心异染色质。异染色质扩散到着丝粒中会阻碍着丝粒功能。 Ohzeki 等人。证明 KAT7 组蛋白乙酰转移酶通过组蛋白周转机制阻止 H3K9-三甲基化酶 Suv39h1 介导的异染色质入侵，从而促进 CENP-A 组装并保留着丝粒功能。
Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long α-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A assembly. Mitotic chromosome misalignment and micronuclei formation increased in the knockout cells and were enhanced when the histone H3-K9 trimethylase Suv39h1 was overproduced. Tethering KAT7 to an ectopic alphoid DNA integration site removed heterochromatic H3K9me3 modification and was sufficient to stimulate new CENP-A or histone H3.3 assembly. Thus, KAT7-containing acetyltransferases associating with the Mis18 complex provides competence for histone turnover/exchange activity on alphoid DNA and prevents Suv39h1-mediated heterochromatin invasion into centromeres. The histone acetyltransferase KAT7 positively regulates centromeric CENP-A assembly Human Mis18 complex is a scaffold for assembly of KAT7 and HJURP, a CENP-A chaperone KAT7 or RSF1 stimulates histone turnover/exchange on alphoid DNA KAT7 antagonizes H3K9-trimethylase Suv39h1-mediated centromere inactivation Human centromeres contain histone H3 variant CENP-A and are flanked by pericentric heterochromatin. Spreading of heterochromatin into the centromere can impede centromere function. Ohzeki et al. demonstrate that the KAT7 histone acetyltransferase promotes CENP-A assembly and preserves centromere function by preventing H3K9-trimethylase Suv39h1-mediated heterochromatin invasion via a histone turnover mechanism.