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

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

  • Cell Rep. 2025 Jan 28;44(1):115148. doi: 10.1016/j.celrep.2024.115148.
Jiaming Zhang 1,  Xuanwen Li 2,  Qi Zhao 2,  Jingzhang Ji 2,  Hongdi Cui 2,  Weibo Hou 2,  Xinyu Wang 3,  Entong Song 2,  Songling Xiao 2,  Shukuan Ling 2,  Shaorong Gao 4,  Xiaoyu Liu 5,  Duancheng Wen 6,  Qingran Kong 7
Affiliations

Affiliations

  • 1 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, Zhejiang, China; Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: jmzhang1225@163.com.
  • 2 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, Zhejiang, China.
  • 3 Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • 4 Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: gaoshaorong@tongji.edu.cn.
  • 5 Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: liuxiaoyu@tongji.edu.cn.
  • 6 Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: duw2001@med.cornell.edu.
  • 7 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, Zhejiang, China. Electronic address: kqr721726@163.com.
PMID: 39932187 DOI: 10.1016/j.celrep.2024.115148
Abstract

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.

Keywords

CP: Developmental biology; CP: Molecular biology; early embryonic development; epigenetic reprogramming; histone variants; maternal H3.3; zygotic genome activation.

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