Single-embryo transcriptomic atlas of oxygen response reveals the critical role of HIF-1 α in prompting embryonic zygotic genome activation

被引：3

作者：

Yao, Fusheng ^{[1
]}

Chu, Meiqiang ^{[1
]}

Xi, Guangyin ^{[1
]}

Dai, Jiage ^{[1
]}

Wang, Zhaochen ^{[1
]}

Hao, Jia ^{[1
]}

Yang, Qianying ^{[1
]}

Wang, Wenjing ^{[1
]}

Tang, Yawen ^{[1
]}

Zhang, Jingyu ^{[1
]}

Yue, Yuan ^{[1
]}

Wang, Yue ^{[1
]}

Xu, Yefen ^{[2
]}

Zhao, Wei ^{[1
]}

Ma, Lizhu ^{[1
]}

Liu, Juan ^{[1
]}

Zhang, Zhenni ^{[1
]}

Tian, Jianhui ^{[1
]}

An, Lei ^{[1
]}

机构：

[1] China Agr Univ, Minist Agr & Rural Affairs, Natl Engn Lab Anim Breeding, Key Lab Anim Genet Breeding & Reprod,Coll Anim Sci, 2 Yuanmingyuan West Rd, Beijing 100193, Peoples R China

[2] Tibet Agr & Anim Husb Coll, Anim Sci Dept, 100 Yucai Rd, Nyingchi 860000, Xizang, Peoples R China

来源：

REDOX BIOLOGY | 2024年 / 72卷

关键词：

Oxygen concentration; Preimplantation mouse embryo; Major ZGA; HIF-1; alpha; Histone modification; Sex dimorphism; X-CHROMOSOME INACTIVATION; GLUCOSE-METABOLISM; REDOX REGULATION; GENE-EXPRESSION; BOVINE EMBRYOS; IN-VIVO; HYPOXIA; TENSION; CULTURE; BLASTOCYST;

D O I：

10.1016/j.redox.2024.103147

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Adaptive response to physiological oxygen levels (physO2; 5% O2) enables embryonic survival in a low-oxygen developmental environment. However, the mechanism underlying the role of physO2 in supporting preimplantation development, remains elusive. Here, we systematically studied oxygen responses of hallmark events in preimplantation development. Focusing on impeded transcriptional upregulation under atmospheric oxygen levels (atmosO2; 20% O2) during the 2-cell stage, we functionally identified a novel role of HIF-1 alpha in promoting major zygotic genome activation by serving as an oxygen-sensitive transcription factor. Moreover, during blastocyst formation, atmosO2 impeded H3K4me3 and H3K27me3 deposition by deregulating histone-lysine methyltransferases, thus impairing X-chromosome inactivation in blastocysts. In addition, we found atmosO2 impedes metabolic shift to glycolysis before blastocyst formation, thus resulting a low-level histone lactylation deposition. Notably, we also reported an increased sex-dimorphic oxygen response of embryos upon preimplantation development. Together, focusing on genetic and epigenetic events that are essential for embryonic survival and development, the present study advances current knowledge of embryonic adaptive responses to physO2, and provides novel insight into mechanism underlying irreversibly impaired developmental potential due to a short-term atmosO2 exposure.

引用

页数：16