EZH2 is required for mouse oocyte meiotic maturation by interacting with and stabilizing spindle assembly checkpoint protein BubRI.
EZH2 is required for mouse oocyte meiotic maturation by interacting with and stabilizing spindle assembly checkpoint protein BubRI.
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EZH2 通过与纺锤体组装检查点蛋白 BubRI 相互作用并使其稳定，是小鼠卵母细胞减数分裂成熟所必需的
DOI：
10.1093/nar/gkw463
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发表时间：
2016-09-19
影响因子：
14.9
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Qu Y;Lu D;Jiang H;Chi X;Zhang H
zeste同源物2增强子（EZH2）使组蛋白H3 Lys 27三甲基化，并在多种生物学过程中发挥关键作用。纺锤体组装检查点蛋白BubR1的稳定性对于体细胞的有丝分裂和卵母细胞的减数分裂是必需的。然而，EZH2在卵母细胞减数分裂成熟中的作用尚不清楚。在这里，我们提出了一个机制EZH2控制BubR1的稳定性在小鼠卵母细胞减数分裂。我们通过证明EZH2调节纺锤体组装和极体I挤出，确定了EZH2的甲基转移酶活性独立功能。EZH2随着卵母细胞从GVBD到MII的进展而增加，而EZH2集中在染色体上。有趣的是，DZNep或GSK 343抑制EZH2甲基转移酶活性并不影响卵母细胞减数分裂成熟。然而，EZH2被吗啉代耗尽导致染色体错位和异常纺锤体组装。此外，EZH2的异位表达导致卵母细胞减数分裂成熟停滞在MI阶段，随后发生染色体错配和非整倍体。从机制上讲，EZH2直接与BubR1相互作用并稳定BubR1，这是一种驱动EZH2参与减数分裂调节的作用。总的来说，我们提供了一个范例，EZH2是需要小鼠卵母细胞减数分裂成熟。
Enhancer of zeste homolog 2 (EZH2) trimethylates histone H3 Lys 27 and plays key roles in a variety of biological processes. Stability of spindle assembly checkpoint protein BubR1 is essential for mitosis in somatic cells and for meiosis in oocytes. However, the role of EZH2 in oocyte meiotic maturation was unknown. Here, we presented a mechanism underlying EZH2 control of BubR1 stability in the meiosis of mouse oocytes. We identified a methyltransferase activity-independent function of EZH2 by demonstrating that EZH2 regulates spindle assembly and the polar body I extrusion. EZH2 was increased with the oocyte progression from GVBD to MII, while EZH2 was concentrated on the chromosomes. Interestingly, inhibition of EZH2 methyltranferase activity by DZNep or GSK343 did not affect oocyte meiotic maturation. However, depletion of EZH2 by morpholino led to chromosome misalignment and abnormal spindle assembly. Furthermore, ectopic expression of EZH2 led to oocyte meiotic maturation arrested at the MI stage followed by chromosome misalignment and aneuploidy. Mechanistically, EZH2 directly interacted with and stabilized BubR1, an effect driving EZH2 into the concert of meiosis regulation. Collectively, we provided a paradigm that EZH2 is required for mouse oocyte meiotic maturation.
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影响因子：
4.3
作者：
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通讯作者：
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影响因子：
4
作者：
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56.9
作者：
Grossniklaus, U;Vielle-Calzada, JP;Gagliano, WB
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PCAF 引发的 EZH2 乙酰化可调节其稳定性并促进肺腺癌进展。
影响因子：
14.9
作者：
Wan J;Zhan J;Li S;Ma J;Xu W;Liu C;Xue X;Xie Y;Fang W;Chin YE;Zhang H
通讯作者：
Zhang H
影响因子：
64.5
作者：
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通讯作者：
Young, RA