HDAC8 drives spindle organization during meiotic maturation of porcine oocytes.
HDAC8 drives spindle organization during meiotic maturation of porcine oocytes.
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HDAC8 在猪卵母细胞减数分裂成熟过程中驱动纺锤体组织
DOI：
10.1111/cpr.13119
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发表时间：
2021-10
影响因子：
8.5
通讯作者：
Xiong B
中科院分区：
文献类型：
--
作者：
Chen Y;Pan C;Lu Y;Miao Y;Xiong B
组蛋白去乙酰化酶8（HDAC 8）是组蛋白去乙酰化酶I家族的成员之一，参与神经元疾病、寄生虫/病毒感染、肿瘤发生等多种生物学过程。然而，其在女性生殖细胞发育过程中的潜在功能尚未完全了解。将HDAC 8靶向siRNA显微注射到GV卵母细胞中以耗尽HDAC 8。PCI-34051用于抑制HDAC 8的酶活性。应用免疫染色、免疫印迹和荧光强度定量来评估HDAC 8去除或抑制对卵母细胞减数分裂成熟、纺锤体/染色体结构、γ-微管蛋白动力学和α-微管蛋白乙酰化水平的影响。我们观察到HDAC 8在猪卵母细胞GV期定位于细胞核，然后在GVBD至M II期移位到纺锤体。HDAC 8的缺失通过显示降低的极体排出率导致卵母细胞减数分裂失败。此外，HDAC 8的耗尽导致异常的纺锤体形态和由于γ-微管蛋白向纺锤体极的有缺陷的募集而导致的染色体错位。值得注意的是，这些减数分裂缺陷是通过使用其特异性抑制剂PCI-34051抑制HDAC 8活性来复制的。然而，HDAC 8的抑制不影响微管稳定性，如通过α微管蛋白的乙酰化水平所评估的。总的来说，我们的研究结果表明，HDAC 8作为一个调节器的纺锤体组装在猪卵母细胞减数分裂成熟。我们的研究结果表明，HDAC 8定位于猪卵母细胞的纺锤体，通过将γ-微管蛋白募集到纺锤体两极参与纺锤体组装，从而驱动卵母细胞减数分裂成熟。HDAC 8的这种功能依赖于其酶活性，并且在哺乳动物中的物种中是保守的。
Histone deacetylase 8 (HDAC8) is one of the class I HDAC family proteins, which participates in the neuronal disorders, parasitic/viral infections, tumorigenesis and many other biological processes. However, its potential function during female germ cell development has not yet been fully understood. HDAC8‐targeting siRNA was microinjected into GV oocytes to deplete HDAC8. PCI‐34051 was used to inhibit the enzyme activity of HDAC8. Immunostaining, immunoblotting and fluorescence intensity quantification were applied to assess the effects of HDAC8 depletion or inhibition on the oocyte meiotic maturation, spindle/chromosome structure, γ‐tubulin dynamics and acetylation level of α‐tubulin. We observed that HDAC8 was localized in the nucleus at GV stage and then translocated to the spindle apparatus from GVBD to M II stages in porcine oocytes. Depletion of HDAC8 led to the oocyte meiotic failure by showing the reduced polar body extrusion rate. In addition, depletion of HDAC8 resulted in aberrant spindle morphologies and misaligned chromosomes due to the defective recruitment of γ‐tubulin to the spindle poles. Notably, these meiotic defects were photocopied by inhibition of HDAC8 activity using its specific inhibitor PCI‐34051. However, inhibition of HDAC8 did not affect microtubule stability as assessed by the acetylation level of α‐tubulin. Collectively, our findings demonstrate that HDAC8 acts as a regulator of spindle assembly during porcine oocyte meiotic maturation. Our findings document that HDAC8 locates to the spindle apparatus in porcine oocytes to take part in the spindle assembly via recruitment of γ‐tubulin to the spindle poles, and hence driving the oocyte meiotic maturation. This function of HDAC8 relies on its enzyme activity and is conserved among species in mammals.
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影响因子：
16
作者：
Hogg SJ;Motorna O;Cluse LA;Johanson TM;Coughlan HD;Raviram R;Myers RM;Costacurta M;Todorovski I;Pijpers L;Bjelosevic S;Williams T;Huskins SN;Kearney CJ;Devlin JR;Fan Z;Jabbari JS;Martin BP;Fareh M;Kelly MJ;Dupéré-Richer D;Sandow JJ;Feran B;Knight D;Khong T;Spencer A;Harrison SJ;Gregory G;Wickramasinghe VO;Webb AI;Taberlay PC;Bromberg KD;Lai A;Papenfuss AT;Smyth GK;Allan RS;Licht JD;Landau DA;Abdel-Wahab O;Shortt J;Vervoort SJ;Johnstone RW
通讯作者：
Johnstone RW
影响因子：
64.5
作者：
STEARNS, T;EVANS, L;KIRSCHNER, M
通讯作者：
KIRSCHNER, M
影响因子：
16.6
作者：
Laband K;Le Borgne R;Edwards F;Stefanutti M;Canman JC;Verbavatz JM;Dumont J
通讯作者：
Dumont J
影响因子：
64.8
作者：
Deardorff, Matthew A.;Bando, Masashige;Nakato, Ryuichiro;Watrin, Erwan;Itoh, Takehiko;Minamino, Masashi;Saitoh, Katsuya;Komata, Makiko;Katou, Yuki;Clark, Dinah;Cole, Kathryn E.;De Baere, Elfride;Decroos, Christophe;Di Donato, Nataliya;Ernst, Sarah;Francey, Lauren J.;Gyftodimou, Yolanda;Hirashima, Kyotaro;Hullings, Melanie;Ishikawa, Yuuichi;Jaulin, Christian;Kaur, Maninder;Kiyono, Tohru;Lombardi, Patrick M.;Magnaghi-Jaulin, Laura;Mortier, Geert R.;Nozaki, Naohito;Petersen, Michael B.;Seimiya, Hiroyuki;Siu, Victoria M.;Suzuki, Yutaka;Takagaki, Kentaro;Wilde, Jonathan J.;Willems, Patrick J.;Prigent, Claude;Gillessen-Kaesbach, Gabriele;Christianson, David W.;Kaiser, Frank J.;Jackson, Laird G.;Hirota, Toru;Krantz, Ian D.;Shirahige, Katsuhiko
通讯作者：
Shirahige, Katsuhiko
DOI：
10.1083/jcb.201607062
发表时间：
2016-12-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bennabi I;Terret ME;Verlhac MH
通讯作者：
Verlhac MH