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Publication : Maternal DNA Methylation Regulates Early Trophoblast Development.

First Author  Branco MR Year  2016
Journal  Dev Cell Volume  36
Issue  2 Pages  152-63
PubMed ID  26812015 Mgi Jnum  J:229091
Mgi Id  MGI:5750799 Doi  10.1016/j.devcel.2015.12.027
Citation  Branco MR, et al. (2016) Maternal DNA Methylation Regulates Early Trophoblast Development. Dev Cell 36(2):152-63
abstractText  Critical roles for DNA methylation in embryonic development are well established, but less is known about its roles during trophoblast development, the extraembryonic lineage that gives rise to the placenta. We dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b mutants. We find that oocyte-derived methylation plays a major role in regulating trophoblast development but that imprinting of the key placental regulator Ascl2 is only partially responsible for these effects. We have identified several methylation-regulated genes associated with trophoblast differentiation that are involved in cell adhesion and migration, potentially affecting trophoblast invasion. Specifically, trophoblast-specific DNA methylation is linked to the silencing of Scml2, a Polycomb Repressive Complex 1 protein that drives loss of cell adhesion in methylation-deficient trophoblast. Our results reveal that maternal DNA methylation controls multiple differentiation-related and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms.
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