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

Simon Andrews, Christel Krueger, Maravillas Mellado-Lopez, Myriam Hemberger, Wendy Dean, Vicente Perez-Garcia and Courtney W. Hanna ()
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Simon Andrews: Babraham Institute
Christel Krueger: Babraham Institute
Maravillas Mellado-Lopez: Centro de Investigación Príncipe Felipe
Myriam Hemberger: University of Calgary
Wendy Dean: University of Calgary
Vicente Perez-Garcia: Centro de Investigación Príncipe Felipe
Courtney W. Hanna: Babraham Institute

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36019-9

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