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Pramel15 facilitates zygotic nuclear DNMT1 degradation and DNA demethylation

Author

Listed:
  • Jiajun Tan

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yingfeng Li

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xiang Li

    (Chinese Academy of Sciences)

  • Xiaoxiao Zhu

    (Chinese Academy of Sciences)

  • Liping Liu

    (University of Texas Southwestern Medical Center)

  • Hua Huang

    (Chinese Academy of Sciences)

  • Jiahua Wei

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hailing Wang

    (Chinese Academy of Sciences)

  • Yong Tian

    (Chinese Academy of Sciences)

  • Zhigao Wang

    (University of South Florida)

  • Zhuqiang Zhang

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Bing Zhu

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

In mammals, global passive demethylation contributes to epigenetic reprogramming during early embryonic development. At this stage, the majority of DNA-methyltransferase 1 (DNMT1) protein is excluded from nucleus, which is considered the primary cause. However, whether the remaining nuclear activity of DNMT1 is regulated by additional mechanisms is unclear. Here, we report that nuclear DNMT1 abundance is finetuned through proteasomal degradation in mouse zygotes. We identify a maternal factor, Pramel15, which targets DNMT1 for degradation via Cullin-RING E3 ligases. Loss of Pramel15 elevates DNMT1 levels in the zygote pronuclei, impairs zygotic DNA demethylation, and causes a stochastic gain of DNA methylation in early embryos. Thus, Pramel15 can modulate the residual level of DNMT1 in the nucleus during zygotic DNA replication, thereby ensuring efficient DNA methylation reprogramming in early embryos.

Suggested Citation

  • Jiajun Tan & Yingfeng Li & Xiang Li & Xiaoxiao Zhu & Liping Liu & Hua Huang & Jiahua Wei & Hailing Wang & Yong Tian & Zhigao Wang & Zhuqiang Zhang & Bing Zhu, 2024. "Pramel15 facilitates zygotic nuclear DNMT1 degradation and DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51614-0
    DOI: 10.1038/s41467-024-51614-0
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