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  3. Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators

Mapping putative enhancers in mouse oocytes and early embryos reveals TCF3/12 as key folliculogenesis regulators

  • Nat Cell Biol. 2024 Jun;26(6):962-974. doi: 10.1038/s41556-024-01422-x.
Bofeng Liu # 1 2,  Yuanlin He # 3 4,  Xiaotong Wu # 2 5,  Zili Lin # 1 2,  Jing Ma # 1 2,  Yuexin Qiu 3,  Yunlong Xiang 1 2,  Feng Kong 1 2,  Fangnong Lai 1 2,  Mrinmoy Pal 6,  Peizhe Wang 7,  Jia Ming 7,  Bingjie Zhang 1 2,  Qiujun Wang 1 2,  Jingyi Wu 1 2,  Weikun Xia 1 2,  Weimin Shen 2 5,  Jie Na 7,  Maria-Elena Torres-Padilla 6,  Jing Li 8 9,  Wei Xie 10 11
Affiliations

Affiliations

  • 1 Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, New Cornerstone Science Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
  • 2 Tsinghua-Peking Center for Life Sciences, Beijing, China.
  • 3 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.
  • 4 Innovation Center of Suzhou Nanjing Medical University, Suzhou, China.
  • 5 Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua University, Beijing, China.
  • 6 Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum München, Munich, Germany.
  • 7 Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, China.
  • 8 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China. ljwth@njmu.edu.cn.
  • 9 Innovation Center of Suzhou Nanjing Medical University, Suzhou, China. ljwth@njmu.edu.cn.
  • 10 Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, New Cornerstone Science Laboratory, School of Life Sciences, Tsinghua University, Beijing, China. xiewei121@tsinghua.edu.cn.
  • 11 Tsinghua-Peking Center for Life Sciences, Beijing, China. xiewei121@tsinghua.edu.cn.
  • # Contributed equally.
PMID: 38839978 DOI: 10.1038/s41556-024-01422-x
Abstract

Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbour prevalent putative enhancers in fully grown oocytes linked to oocyte-specific genes and repeat activation. Embryo-specific enhancers are primed before zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis, TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting transcription factors that underpin the development of mammalian oocytes and early embryos.

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