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  3. The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1

The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1

  • Nat Struct Mol Biol. 2025 Apr 17. doi: 10.1038/s41594-025-01538-0.
Chengpeng Xu # 1 2,  Dandan Qin # 1,  Xukun Lu # 3,  Qianqian Qi # 4,  Yu Wu 1 2,  Qizhi Wang 1 2,  Zhuo Han 4,  Xiaoqing Nie 1,  Yongmei Jiang 4,  Dong Deng 5,  Wei Xie 6,  Zheng Gao 7,  Lei Li 8 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Organ Regeneration and Reconstruction, Beijing Institute for Stem Cell and Regenerative Medicine, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
  • 3 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
  • 4 Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, China.
  • 5 Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, China. dengd@scu.edu.cn.
  • 6 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.
  • 7 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Key Laboratory for Reproductive Medicine of Guangdong Province, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. gaozheng@gzhmu.edu.cn.
  • 8 State Key Laboratory of Organ Regeneration and Reconstruction, Beijing Institute for Stem Cell and Regenerative Medicine, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. lil@ioz.ac.cn.
  • 9 University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China. lil@ioz.ac.cn.
  • # Contributed equally.
PMID: 40247146 DOI: 10.1038/s41594-025-01538-0
Abstract

How cytoplasmic regulators control nuclear events in mammalian oocytes and early embryos remains largely enigmatic. We previously identified a subcortical maternal complex (SCMC) that specifically resides in the cytoplasm of mammalian oocytes and early embryos but is also involved in nuclear events. Nevertheless, how the cytoplasmic SCMC exerts its role in nuclear processes remains unknown. In this study, we unveil SPIN1, a histone methylation reader, as a novel member of the SCMC. The SCMC component FILIA tightly regulates the expression and cytoplasmic localization of SPIN1 through direct interaction. When the expression of FILIA is decreased because of genetic mutations of SCMC genes, SPIN1 expression is dramatically reduced but the residual SPIN1 translocates into the nucleus. The abnormal nuclear presence of SPIN1 impairs H3K4me3 reprogramming, zygotic genome activation and physiological embryonic development. Inhibiting the interaction between SPIN1 and H3K4me3 partially rescues the abnormal phenotype in FILIA-null embryos. Mechanistically, SPIN1 partially perturbs the demethylation process by competing with KDM5B for binding to H3K4me3. Collectively, our work highlights the complexity of the mammalian SCMC and oocyte-to-embryo transition, revealing an intricate regulatory mechanism that facilitates the smooth progression of this process.

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