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<p>Bivalency regulates developmental genes during lineage commitment. However, mechanisms governing bivalent domain establishment, maintenance and resolution in early embryogenesis remain unclear. Here we comprehensively trace bivalent chromatin remodelling throughout mouse peri-implantation development, revealing bifurcated establishment modes that partition epiblast and primitive endoderm regulatory programmes. We identify transiently maintained bivalent domains (TB domains) enriched in the epiblast, where gradual resolution fine-tunes pluripotency progression. Through targeted screening in embryos, we uncover 22 TB domain regulators, including the essential factor ZBTB17. Genetic ablation or degradation of ZBTB17 causes peri-implantation arrest. Mechanistically, ZBTB17 collaborates with KDM6A/B to resolve bivalency by removing H3K27me3 and priming the activation of key pluripotency genes. Remarkably, TB domain dynamics are evolutionarily shared in human pluripotent transitions, with ZBTB17 involvement despite species differences. Our work establishes a framework for bivalent chromatin regulation in early mammalian development and elucidates how its resolution precisely controls lineage commitment.</p>

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Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Yanhe Li,
  • Jincan He,
  • Yingdong Liu,
  • Yi Hui,
  • Shanyao Liu,
  • Yalin Zhang,
  • Yan Xiong,
  • Tingting Xu,
  • Ziwen Xu,
  • Zhuoao Zhang,
  • Yan Zhang,
  • Guang Yang,
  • Jia Zhao,
  • Dandan Bai,
  • Xinyi Lei,
  • Xiaochen Kou,
  • Yanhong Zhao,
  • Jing Du,
  • Zheng Guo,
  • Jiqing Yin,
  • Xiaoqing Zhang,
  • Congling Xu,
  • Yawei Gao,
  • Miaoxin Chen,
  • Hong Wang,
  • Cizhong Jiang,
  • Shaorong Gao,
  • Wenqiang Liu

摘要

Bivalency regulates developmental genes during lineage commitment. However, mechanisms governing bivalent domain establishment, maintenance and resolution in early embryogenesis remain unclear. Here we comprehensively trace bivalent chromatin remodelling throughout mouse peri-implantation development, revealing bifurcated establishment modes that partition epiblast and primitive endoderm regulatory programmes. We identify transiently maintained bivalent domains (TB domains) enriched in the epiblast, where gradual resolution fine-tunes pluripotency progression. Through targeted screening in embryos, we uncover 22 TB domain regulators, including the essential factor ZBTB17. Genetic ablation or degradation of ZBTB17 causes peri-implantation arrest. Mechanistically, ZBTB17 collaborates with KDM6A/B to resolve bivalency by removing H3K27me3 and priming the activation of key pluripotency genes. Remarkably, TB domain dynamics are evolutionarily shared in human pluripotent transitions, with ZBTB17 involvement despite species differences. Our work establishes a framework for bivalent chromatin regulation in early mammalian development and elucidates how its resolution precisely controls lineage commitment.