title: Characterization of Histone Modifications Associated with Inactive X-Chromosome in Trophoblast Stem Cells, eXtra-Embryonic Endoderm Cells and in In Vitro Derived Undifferentiated and Differentiated Epiblast Like Stem Cells.
abstract: In mouse, X-chromosome inactivation (XCI) can either be imprinted or random. Imprinted XCI (iXCI) is considered unstable and depending on continuous Xist expression, whereas random XCI (rXCI) is stably maintained even in the absence of Xist. Here we have systematically examined epigenetic modifications associated with the inactive X-chromosome (Xi) in Trophoblast Stem cells, eXtra-Embryonic Endoderm Cells, undifferentiated and differentiated Epiblast Like Stem Cells in order to understand intrinsic differences in epigenetic mechanisms involved in silencing of the inactive X-chromosome in lineages presenting iXCI and rXCI. Whereas euchromatic histone modifications are predominantly lost from the Xi territory in all cell types, the accumulation of heterochromatic modifications diverges in between the analysed cell lineages. Particularly, only the Xi of multipotent Trophoblast (iXCI) and Epiblast stem cells (rXCI) display a visible accumulation of Polycomb Repressive Complexes (PRCs), in contrast to the Xi in differentiated Epiblast Like Stem Cells and eXtra-embryonic Endoderm cells. Despite this, the histone modifications catalysed by PRCs, ubH2AK119 and H3K27me3, remain the best heterochromatic markers for the Xi in all assessed lineages. Heterochromatic chromatin modifications associated with the Xi are a reflection of the epigenetic landscape of the entire genome of the assessed cell regardless whether XCI is imprinted or random.
authors.affiliation: Erasmus MC, Department of Developmental Biology, Rotterdam, The Netherlands.
authors.forename: Cathérine
authors.identifier: http://orcid.org/0000-0002-6228-1202
authors.initials: C
authors.lastname: Dupont
authors.affiliation: Erasmus MC, Department of Developmental Biology, Rotterdam, The Netherlands.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Maduro
authors.affiliation: Erasmus MC, Department of Developmental Biology, Rotterdam, The Netherlands.
authors.forename: Hannah
authors.initials: H
authors.lastname: Den Braanker
authors.affiliation: Erasmus MC, Department of Developmental Biology, Rotterdam, The Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: Boers
authors.affiliation: Erasmus MC, Department of Developmental Biology, Rotterdam, The Netherlands.
authors.forename: Dorota
authors.initials: D
authors.lastname: Kurek
authors.affiliation: Erasmus MC, Department of Developmental Biology, Rotterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Gribnau
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism*; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D014960:X Chromosome / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D006657:Histones