首页|Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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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,H3K181ac 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.

mammalian preimplantation developmentlactateepigenetic remodelinghistone lactylationzygotic genome activation

Jingyu Li、Weibo Hou、Qi Zhao、Wei Han、Hongdi Cui、Songling Xiao、Ling Zhu、Jiadan Qu、Xiaoyu Liu、Weitao Cong、Jingling Shen、Yuzheng Zhao、Shaorong Gao、Guoning Huang、Qingran Kong

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Chongqing Key Laboratory of Human Embryo Engineering,Center for Reproductive Medicine,Chongqing Health Center for Women and Children,Women and Children's Hospital of Chongqing Medical University,Chongqing 400010,China

Oujiang Laboratory,Zhejiang Provincial Key Laboratory of Medical Genetics,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China

Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China

School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou 325035,China

Institute of Life Sciences,College of Life and Environmental Sciences,Wenzhou University,Wenzhou 325035,China

Optogenetics &Synthetic Biology Interdisciplinary Research Center,State Key Laboratory of Bioreactor Engineering,Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism,School of Pharmacy,East China University of Science and Technology,Shanghai 2000237,China

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Basic public welfare research program of Zhejiang ProvinceChongqing science and Health Joint ProjectNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

LY22C1200012021MSXM0723237086282301880

2024

10.1093/nsr/nwad295

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ISSN：
年,卷(期)：2024.11(2)
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