Interspecific hybrids reveal a deeply conserved nuclear role of EIF1A-family proteins in zygotic genome activation
Year: 2026
Type: preprint
Abstract: Zygotic genome activation (ZGA) launches inaugural gene expression and autonomous development of the embryo. Yet, conserved regulators of ZGA among different mammals remain poorly defined. Here, we generated interspecific hybrid embryos to place distant mammalian genomes in a shared maternal cytoplasm. These hybrids undergo cleavage and transcriptional activation from divergent parental genomes. Comparative transcriptomics identifies a core set of zygotic genes reproducibly activated across different hybrid contexts, including the Eif1a-like family. Depletion of EIF1A-like proteins disrupts ZGA and preimplantation development in mouse, pig and cattle embryos. Although best known for translation initiation, these proteins contain a conserved nuclear localization signal and translocate to the nucleus at the onset of major ZGA. Further studies revealed that they occupy promoters of nearly all ZGA genes and MERVL/MT2 retrotransposons, required for local chromatin accessibility. These findings uncover a conserved nuclear licensing function for EIF1A-family proteins in zygotic genome activation among divergent mammalian embryos.
Authors: Ding Qiu, Dengfeng Bi, Zhiheng Yuan, Zhenghao Qiao, Zhongcheng Zhou, Zeling Wang, Yunlong Li, Zhenyu Zhong, Yibei Wu, Ziyan Rong, Lijun Deng, Xiaohua Lu, Tong Wang, Yongkang Jia, Jiemei Chen, Weiwei Liu, Sheng Wang, Xiaozhong Zhang, Tianyu Zhang, Ming Wang, Quanyong Zhang, Xiaoyun Wang, Wenhua Yu, Yanna Dang, Chao Liu, Wei Li, Zhiheng Chen, Ling Sun, Siqi Gui, Jingcheng Zhang, Jie Li, Yunkun Dang, Yuan Qin, Tiejun Zhang, Hao Chen, Qianqian Sha, Yanfang Wang, Na Yang, Wei Xie, Kai Chen, Jianguo Zhao, Yang Yu
Institutions: Guangzhou Women and Children Medical Center, Guangzhou Medical University, Chinese Academy of Sciences, Chinese Academy of Agricultural Sciences, Institute of Animal Sciences, Institute of Zoology, Beijing Institute for Stem Cell and Regenerative Medicine, Cancer Hospital of Shantou University Medical College, Yunnan University, Fujian Agriculture and Forestry University, Nankai University, State Key Laboratory of Medicinal Chemical Biology, Institute of Biophysics, Guangzhou University, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Center for Life Sciences, Tsinghua University, Northwest A&F University, Institute of Microbiology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7224079057