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Dynamic antagonism between key repressive pathways maintains the placental epigenome

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Item Type:Article
Title:Dynamic antagonism between key repressive pathways maintains the placental epigenome
Creators Name:Weigert, R. and Hetzel, S. and Bailly, N. and Haggerty, C. and Ilik, I.A. and Yung, P.Y.K. and Navarro, C. and Bolondi, A. and Kumar, A.S. and Anania, C. and Brändl, B. and Meierhofer, D. and Lupianez, D.G. and Müller, F.J. and Aktas, T. and Elsässer, S.J. and Kretzmer, H. and Smith, Z.D. and Meissner, A.
Abstract:DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains. Here, to better understand this unusual landscape's molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse trophoblast stem cells. We find that the extra-embryonic epigenome reflects ongoing and dynamic de novo methyltransferase recruitment, which is continuously antagonized by Polycomb to maintain intermediate, locally disordered methylation. Despite its disorganized molecular appearance, our data point to a highly controlled equilibrium between counteracting repressors within extra-embryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation.
Keywords:Embryogenesis, Epigenomics, Stem Cells, Animals, Mice
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:579–591
Date:April 2023
Official Publication:https://doi.org/10.1038/s41556-023-01114-y
PubMed:View item in PubMed

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