文献类型：期刊文献

英文题名：Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

作者：Li, Jingyu[1];Hou, Weibo[2];Zhao, Qi[2];Han, Wei[1];Cui, Hongdi[2];Xiao, Songling[2];Zhu, Ling[1];Qu, Jiadan[1];Liu, Xiaoyu[3];Cong, Weitao[4];Shen, Jingling[5];Zhao, Yuzheng[6];Gao, Shaorong[3];Huang, Guoning[1];Kong, Qingran[2]

机构：[1]Chongqing Med Univ, Ctr Reprod Med, Chongqing Hlth Ctr Women & Children, Chongqing Key Lab Human Embryo Engn,Women & Childr, Chongqing 400010, Peoples R China;[2]Wenzhou Med Univ, Sch Lab Med & Life Sci, Oujiang Lab, Zhejiang Prov Key Lab Med Genet, Wenzhou 325035, Peoples R China;[3]Tongji Univ, Frontier Sci Ctr Stem Cell Res, Sch Life Sci & Technol, Shanghai 200092, Peoples R China;[4]Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China;[5]Wenzhou Univ, Inst Life Sci, Coll Life & Environm Sci, Wenzhou 325035, Peoples R China;[6]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm,State Key Lab Bioreactor Engn, Shanghai 2000237, Peoples R China

年份：2024

卷号：11

期号：2

外文期刊名：NATIONAL SCIENCE REVIEW

收录：;EI(收录号：20240715534694);WOS:【SCI-EXPANDED(收录号:WOS:001157690300001)】；

基金：This work was supported by the Basic public welfare research program of Zhejiang Province (LY22C120001), the Chongqing Science and Health Joint Project (2021MSXM072) and the National Natural Science Foundation of China (32370862, 82301880)

语种：英文

外文关键词：mammalian preimplantation development; lactate; epigenetic remodeling; histone lactylation; zygotic genome activation

摘要：Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-CoA and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.