Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation

Summary: Zygotic genome activation (ZGA) initiates transcription in early embryogenesis and requires extensive chromatin remodeling, including rapid incorporation of the histone variant H3.3. The distinct sources of H3.3 from paternal and maternal alleles (paH3.3 and maH3.3) complicate tracking thei...

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Main Authors: Jiaming Zhang, Xuanwen Li, Qi Zhao, Jingzhang Ji, Hongdi Cui, Weibo Hou, Xinyu Wang, Entong Song, Songling Xiao, Shukuan Ling, Shaorong Gao, Xiaoyu Liu, Duancheng Wen, Qingran Kong
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724014992
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author Jiaming Zhang
Xuanwen Li
Qi Zhao
Jingzhang Ji
Hongdi Cui
Weibo Hou
Xinyu Wang
Entong Song
Songling Xiao
Shukuan Ling
Shaorong Gao
Xiaoyu Liu
Duancheng Wen
Qingran Kong
author_facet Jiaming Zhang
Xuanwen Li
Qi Zhao
Jingzhang Ji
Hongdi Cui
Weibo Hou
Xinyu Wang
Entong Song
Songling Xiao
Shukuan Ling
Shaorong Gao
Xiaoyu Liu
Duancheng Wen
Qingran Kong
author_sort Jiaming Zhang
collection DOAJ
description Summary: Zygotic genome activation (ZGA) initiates transcription in early embryogenesis and requires extensive chromatin remodeling, including rapid incorporation of the histone variant H3.3. The distinct sources of H3.3 from paternal and maternal alleles (paH3.3 and maH3.3) complicate tracking their individual contributions. Here, using an H3.3B-hemagglutinin (HA)-tagged mouse model, we profile the temporal dynamics of paH3.3 and maH3.3, revealing a unique pattern of maH3.3 enrichment at the promoter regions from zygotes to 2-cell embryos, highlighting the crucial role of maternally stored H3.3 mRNAs and proteins (mH3.3) in pre-implantation development. Knockdown of mH3.3 compromises cleavage and minor ZGA. Mechanistically, mH3.3 facilitates minor ZGA through H3.3S31ph-dependent H3K27ac deposition. Profiling of H3.3 landscape in parthenogenetic (PG) and androgenetic (AG) embryos highlights the role of mH3.3 in remodeling the paternal genome by establishing H3K27ac. These findings demonstrate that mH3.3-mediated parental chromatin reprogramming is essential for orchestrating minor ZGA.
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spelling doaj-art-9e7505f75d8b43888672ff11de07af3c2025-08-20T02:51:18ZengElsevierCell Reports2211-12472025-01-0144111514810.1016/j.celrep.2024.115148Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activationJiaming Zhang0Xuanwen Li1Qi Zhao2Jingzhang Ji3Hongdi Cui4Weibo Hou5Xinyu Wang6Entong Song7Songling Xiao8Shukuan Ling9Shaorong Gao10Xiaoyu Liu11Duancheng Wen12Qingran Kong13Oujiang 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, Zhejiang, China; Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding authorOujiang 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, Zhejiang, ChinaOujiang 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, Zhejiang, ChinaOujiang 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, Zhejiang, ChinaOujiang 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, Zhejiang, ChinaOujiang 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, Zhejiang, ChinaFrontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaOujiang 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, Zhejiang, ChinaOujiang 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, Zhejiang, ChinaOujiang 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, Zhejiang, ChinaFrontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Corresponding authorFrontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Corresponding authorRonald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Corresponding authorOujiang 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, Zhejiang, China; Corresponding authorSummary: Zygotic genome activation (ZGA) initiates transcription in early embryogenesis and requires extensive chromatin remodeling, including rapid incorporation of the histone variant H3.3. The distinct sources of H3.3 from paternal and maternal alleles (paH3.3 and maH3.3) complicate tracking their individual contributions. Here, using an H3.3B-hemagglutinin (HA)-tagged mouse model, we profile the temporal dynamics of paH3.3 and maH3.3, revealing a unique pattern of maH3.3 enrichment at the promoter regions from zygotes to 2-cell embryos, highlighting the crucial role of maternally stored H3.3 mRNAs and proteins (mH3.3) in pre-implantation development. Knockdown of mH3.3 compromises cleavage and minor ZGA. Mechanistically, mH3.3 facilitates minor ZGA through H3.3S31ph-dependent H3K27ac deposition. Profiling of H3.3 landscape in parthenogenetic (PG) and androgenetic (AG) embryos highlights the role of mH3.3 in remodeling the paternal genome by establishing H3K27ac. These findings demonstrate that mH3.3-mediated parental chromatin reprogramming is essential for orchestrating minor ZGA.http://www.sciencedirect.com/science/article/pii/S2211124724014992CP: Molecular biologyCP: Developmental biology
spellingShingle Jiaming Zhang
Xuanwen Li
Qi Zhao
Jingzhang Ji
Hongdi Cui
Weibo Hou
Xinyu Wang
Entong Song
Songling Xiao
Shukuan Ling
Shaorong Gao
Xiaoyu Liu
Duancheng Wen
Qingran Kong
Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation
Cell Reports
CP: Molecular biology
CP: Developmental biology
title Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation
title_full Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation
title_fullStr Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation
title_full_unstemmed Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation
title_short Acetylation at lysine 27 on maternal H3.3 regulates minor zygotic genome activation
title_sort acetylation at lysine 27 on maternal h3 3 regulates minor zygotic genome activation
topic CP: Molecular biology
CP: Developmental biology
url http://www.sciencedirect.com/science/article/pii/S2211124724014992
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