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Mechanisms and function of de novo DNA methylation in placental development [RNA-Seq]

ABSTRACT: Mechanisms and function of de novo DNA methylation in placental development [RNA-Seq]

PROVIDER: PRJNA839374 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19268100.fastq.gz	Fastqsanger.gz
	SRR19268079.fastq.gz	Fastqsanger.gz
	SRR19268080.fastq.gz	Fastqsanger.gz
	SRR19268081.fastq.gz	Fastqsanger.gz
	SRR19268082.fastq.gz	Fastqsanger.gz

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Mechanisms and function of de novo DNA methylation in placental development [PBAT]

Project description: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 demonstrate that each of the DNMTs is required to establish the placental methylome and is distinctly targeted to genome based on underlying chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired development of the placental maternal-foetal interface. Critically, loss of DNA methylation in the placenta did not lead to abnormalities in lineage specification or cell identity, but to defective formation and vascularisation of the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental trophoblast cells, we were able to rescue the placental phenotype and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that the principal function of DNA methylation during embryogenesis is to regulate placental function, which in turn is critical for embryo survival.

2022-12-15 | GSE203292 | GEO