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EED and IgG (as control) co-immunoprecipitation of wild type embryonic stem cells (ESCs), with 3 biological replicates per condition.

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 extraembryonic lineages display non-canonical, globally intermediate DNA methylation levels that includes disruption of local Polycomb domains. To better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse Trophoblast Stem Cells (TSCs). We find that the extraembryonic 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 extraembryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation.

INSTRUMENT(S): timsTOF SCP

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: David Meierhofer

LAB HEAD: Alexander Meissner

PROVIDER: PXD039719 | Pride | 2023-02-06

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	DIA_NN_files.zip	Other
	ES_EED_rep_1_S1-D1_1_1534.d.dia	Other
	ES_EED_rep_1_S1-D1_1_1534.d.dia.quant	Other
	ES_EED_rep_2_S1-E1_1_1535.d.dia	Other
	ES_EED_rep_2_S1-E1_1_1535.d.dia.quant	Other

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Dynamic antagonism between key repressive pathways maintains the placental epigenome -1

Project description: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 extraembryonic lineages display non-canonical, globally intermediate DNA methylation levels that includes disruption of local Polycomb domains. To better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse Trophoblast Stem Cells (TSCs). We find that the extraembryonic 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 extraembryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation. Dataset 1: EED co-immunoprecipitation of wild type mouse trophoblast stem cells (TSCs) and Eed knockout TSCs as control, with 3 biological replicates per condition.

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