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Loss of DNA methylation disrupts syncytiotrophoblast development: Proposed consequences of aberrant germline gene activation

Accepted version
Peer-reviewed

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Abstract

DNA methylation is a repressive epigenetic modification that is essential for development and its disruption is widely implicated in disease. Yet, remarkably, ablation of DNA methylation in transgenic mouse models has limited impact on transcriptional states. Across multiple tissues and developmental contexts, the predominant transcriptional signature upon loss of DNA methylation is the de-repression of a subset of germline genes, normally expressed in gametogenesis. We recently reported loss of de novo DNA methyltransferase DNMT3B resulted in up-regulation of germline genes and impaired syncytiotrophoblast formation in the murine placenta. This defect led to embryonic lethality. We hypothesize that de-repression of germline genes in the Dnmt3b knockout underpins aspects of the placental phenotype by interfering with normal developmental processes. Specifically, we discuss molecular mechanisms by which aberrant expression of the piRNA pathway, meiotic proteins or germline transcriptional regulators may disrupt syncytiotrophoblast development.

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Keywords

Germ Cells, Trophoblasts, Placenta, Animals, Mice, Transgenic, Mice, DNA Methylation, Pregnancy, Female, Transcriptional Activation, DNA (Cytosine-5-)-Methyltransferases

Journal Title

BioEssays

Conference Name

Journal ISSN

0265-9247
1521-1878

Volume Title

Publisher

Wiley
Sponsorship
Wellcome Trust (222582/Z/21/Z)