Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B.
Simon R AndrewsChristel KruegerMaravillas Mellado-LopezMyriam HembergerWendy DeanVicente Perez-GarciaCourtney W HannaPublished in: Nature communications (2023)
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.
Keyphrases
- dna methylation
- genome wide
- gene expression
- copy number
- induced apoptosis
- pregnancy outcomes
- poor prognosis
- stem cells
- physical activity
- metabolic syndrome
- skeletal muscle
- adipose tissue
- long non coding rna
- gestational age
- signaling pathway
- cell proliferation
- cancer therapy
- oxidative stress
- high fat diet induced
- insulin resistance