EZH2 is essential for development of mouse preimplantation embryos
Xian-Ju Huang A , Xuguang Wang A B , Xueshan Ma A C , Shao-Chen Sun A , Xiaolong Zhou A , Chengcheng Zhu A and Honglin Liu D
+ Author Affiliations
- Author Affiliations
A College of Animal Science and Technology, Nanjing Agricultural University, Weigang No.1, Nanjing 210095, China.
B Animal Science College, Xinjiang Agricultural University, Nongda rode No.311, Wulumuqi, Xinjiang 830052, China.
C State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Peking University People’s Hospital, Beichen weste rode No.1, Chaoyang district, Beijing 100101, China.
D Corresponding author. Email: liuhonglin@263.net
Reproduction, Fertility and Development 26(8) 1166-1175 https://doi.org/10.1071/RD13169
Submitted: 6 June 2013 Accepted: 6 September 2013 Published: 24 October 2013
Abstract
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.
Additional keywords: de novo, growth retardation, histone modification.
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