Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation

Yi-Ran Zhang; Shi-Meng Guo; Xiao-Yan Shi; Yi-Wen Ding; Huai-Biao Li; Lei Li; Jia-Wei Xu; Ximiao He; Bing-Xin Ma; Ying Yin; Li-Quan Zhou

doi:10.1016/j.celrep.2024.115215

Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation

Cell Rep. 2025 Jan 16;44(1):115215. doi: 10.1016/j.celrep.2024.115215. Online ahead of print.

Authors

Yi-Ran Zhang¹, Shi-Meng Guo², Xiao-Yan Shi¹, Yi-Wen Ding¹, Huai-Biao Li¹, Lei Li³, Jia-Wei Xu⁴, Ximiao He⁵, Bing-Xin Ma⁶, Ying Yin⁷, Li-Quan Zhou⁸

Affiliations

¹ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
² Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing 400012, P.R. China.
³ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
⁴ NHC Key Laboratory of Birth Defect Prevention, Zhengzhou, Henan 451163, P.R. China.
⁵ Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
⁶ Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China. Electronic address: [email protected].
⁷ Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China. Electronic address: [email protected].
⁸ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; NHC Key Laboratory of Birth Defect Prevention, Zhengzhou, Henan 451163, P.R. China. Electronic address: [email protected].

PMID: 39823229
DOI: 10.1016/j.celrep.2024.115215

Abstract

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages. Gene collections with different expression patterns are obtained, with genes mainly transcribed at the mouse early/late 2-cell stage designated as zygotic genome activation-early/late 2-cell (ZGA-E2C/L2C). ZGA-E2C genes are short and have low promoter CpG density. Protein translation/degradation not only regulates transcription activity through stepwise orchestration of histone modifications, transcriptional initiation, and elongation in early mouse embryos but also controls on/off switching of ZGA-E2C/L2C genes in maternal aged mouse embryos. Genes mainly transcribed at the mouse 2-cell stage can also be transcribed as early as the human 2-cell stage.

Keywords: CP: Developmental biology; CP: Molecular biology; embryo; maternal aging; preimplantation; transcription activity; zygotic genome activation.