EZH2 is essential for development of mouse preimplantation embryos
EZH2 is essential for development of mouse preimplantation embryos
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EZH2 对于小鼠植入前胚胎的发育至关重要
DOI：
10.1071/rd13169
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发表时间：
2014-01-01
影响因子：
1.9
通讯作者：
Liu, Honglin
中科院分区：
文献类型：
--
作者：
Huang, Xian-Ju;Wang, Xuguang;Liu, Honglin
ZAST同源增强子2(Ezh2)是小鼠早期植入前胚胎发育所必需的。Ezh2基因的缺失会导致小鼠胚胎死亡。EZH2基因缺陷的胚胎表现出生长潜能受损，Ezh2缺失的胚胎干细胞(ES细胞)建立缺陷，滋养层黏附和分化为巨细胞。我们用放线菌酮(CHX)或微量注射短干扰RNA(SiRNA)来限制胚胎着床前Ezh2的表达，研究了Ezh2是否在早期阶段控制了胚胎的命运。ChX抑制受精卵中EZH2蛋白的从头合成，这表明EZH2在受精后阶段需要从头合成。我们发现，在原核阶段Ezh2的缺失会导致严重的生长迟缓和囊胚形成减少。在注射Ezh2 siRNA的胚胎中，与多能性相关的标记Oct4、Sox2和Nanog的表达显著降低。此外，Ezh2缺失还诱导了与胚层分化相关的基因GATA6、Hoxb1和Hand1的表达上调。最后，Ezh2基因敲除后的囊胚细胞凋亡率增加。组蛋白H3-赖氨酸27去甲基化和三甲基化(H3K27me2/3)的修饰在Ezh2 siRNA胚胎中显著减少。我们认为，Ezh2通过对表观遗传修饰和细胞凋亡的调控，对早期植入前胚胎的发育起着至关重要的作用。
Enhancer of zeste homologue 2 (Ezh2) is essential for the development of the early mouse preimplantation embryo. Loss of Ezh2 results in embryonic lethality in mice. Ezh2-deficient embryos display impaired outgrowth potential, defective establishment of Ezh2-null embryonic stem (ES) cells and adherence and differentiation of the trophoblast layer into giant cells. We investigated if Ezh2 controls the fate of embryos at an earlier stage by treating with cycloheximide (CHX) or microinjecting short interfering RNA (siRNA) to restrict embryonic Ezh2 expression during preimplantation. CHX inhibited de novo EZH2 protein synthesis in zygotes, suggesting that EZH2 requires de novo synthesis during post-fertilisation stages. We found that loss of Ezh2 at the pronuclear stage caused severe growth retardation and reduced blastocyst formation. Expression of the pluripotency-associated markers Oct4, Sox2 and Nanog were significantly decreased in embryos that had been injected with Ezh2 siRNA. In addition, Ezh2 loss induced upregulated expression of genes related to the differentiation of germ layers, including Gata6, Hoxb1 and Hand1. Finally, apoptosis was increased in the blastocyst embryos with Ezh2 knockdown. Modification of histone H3-Lysine 27 de-methylation and tri-methylation (H3K27me2/3) was strongly reduced in Ezh2 siRNA embryos. We conclude that Ezh2 is essential for early preimplantation embryo development through the regulation of epigenetic modification and apoptosis.