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Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B

Author

Listed:
  • Simon Andrews

    (Babraham Institute)

  • Christel Krueger

    (Babraham Institute
    Babraham Institute
    Altos Labs Cambridge Institute)

  • Maravillas Mellado-Lopez

    (Centro de Investigación Príncipe Felipe)

  • Myriam Hemberger

    (University of Calgary
    University of Calgary
    University of Calgary)

  • Wendy Dean

    (University of Calgary
    University of Calgary)

  • Vicente Perez-Garcia

    (Centro de Investigación Príncipe Felipe)

  • Courtney W. Hanna

    (Babraham Institute
    University of Cambridge
    University of Cambridge)

Abstract

DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We find that each DNMT establishes unique aspects of the placental methylome through targeting to distinct chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired formation of the maternal-foetal interface in the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental cells, the placental phenotype was rescued and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that de novo DNA methylation by DNMT3B during embryogenesis is principally required to regulate placental development and function, which in turn is critical for embryo survival.

Suggested Citation

  • Simon Andrews & Christel Krueger & Maravillas Mellado-Lopez & Myriam Hemberger & Wendy Dean & Vicente Perez-Garcia & Courtney W. Hanna, 2023. "Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36019-9
    DOI: 10.1038/s41467-023-36019-9
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    1. Qing Li & Jiansen Lu & Xidi Yin & Yunjian Chang & Chao Wang & Meng Yan & Li Feng & Yanbo Cheng & Yun Gao & Beiying Xu & Yao Zhang & Yingyi Wang & Guizhong Cui & Luang Xu & Yidi Sun & Rong Zeng & Yixue, 2023. "Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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