title: Global chromatin architecture reflects pluripotency and lineage commitment in the early mouse embryo.
abstract: An open chromatin architecture devoid of compact chromatin is thought to be associated with pluripotency in embryonic stem cells. Establishing this distinct epigenetic state may also be required for somatic cell reprogramming. However, there has been little direct examination of global structural domains of chromatin during the founding and loss of pluripotency that occurs in preimplantation mouse development. Here, we used electron spectroscopic imaging to examine large-scale chromatin structural changes during the transition from one-cell to early postimplantation stage embryos. In one-cell embryos chromatin was extensively dispersed with no noticeable accumulation at the nuclear envelope. Major changes were observed from one-cell to two-cell stage embryos, where chromatin became confined to discrete blocks of compaction and with an increased concentration at the nuclear envelope. In eight-cell embryos and pluripotent epiblast cells, chromatin was primarily distributed as an extended meshwork of uncompacted fibres and was indistinguishable from chromatin organization in embryonic stem cells. In contrast, lineage-committed trophectoderm and primitive endoderm cells, and the stem cell lines derived from these tissues, displayed higher levels of chromatin compaction, suggesting an association between developmental potential and chromatin organisation. We examined this association in vivo and found that deletion of Oct4, a factor required for pluripotency, caused the formation of large blocks of compact chromatin in putative epiblast cells. Together, these studies show that an open chromatin architecture is established in the embryonic lineages during development and is sufficient to distinguish pluripotent cells from tissue-restricted progenitor cells.
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Kashif
authors.initials: K
authors.lastname: Ahmed
authors.forename: Hesam
authors.initials: H
authors.lastname: Dehghani
authors.forename: Peter
authors.initials: P
authors.lastname: Rugg-Gunn
authors.forename: Eden
authors.initials: E
authors.lastname: Fussner
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.forename: David P
authors.initials: DP
authors.lastname: Bazett-Jones
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure*; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D002843:Chromatin