title: Dynamic Reorganization of Extremely Long-Range Promoter-Promoter Interactions between Two States of Pluripotency.
abstract: Serum-to-2i interconversion of mouse embryonic stem cells (mESCs) is a valuable in vitro model for early embryonic development. To assess whether 3D chromatin organization changes during this transition, we established Capture Hi-C with target-sequence enrichment of DNase I hypersensitive sites. We detected extremely long-range intra- and inter-chromosomal interactions between a small subset of H3K27me3 marked bivalent promoters involving the Hox clusters in serum-grown cells. Notably, these promoter-mediated interactions are not present in 2i ground-state pluripotent mESCs but appear upon their further development into primed-like serum mESCs. Reverting serum mESCs to ground-state 2i mESCs removes these promoter-promoter interactions in a spatiotemporal manner. H3K27me3, which is largely absent at bivalent promoters in ground-state 2i mESCs, is necessary, but not sufficient, to establish these interactions, as confirmed by Capture Hi-C on Eed(-/-) serum mESCs. Our results implicate H3K27me3 and PRC2 as critical players in chromatin alteration during priming of ESCs for differentiation.
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Onkar
authors.initials: O
authors.lastname: Joshi
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Shuang-Yin
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kuznetsova
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Atlasi
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Tianran
authors.initials: T
authors.lastname: Peng
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale, Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Fabre
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Habibi
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Jani
authors.initials: J
authors.lastname: Shaik
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Sadia
authors.initials: S
authors.lastname: Saeed
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands.
authors.forename: Lusy
authors.initials: L
authors.lastname: Handoko
authors.affiliation: Roche NimbleGen, Incorporated, 500 South Rosa Road, Madison, WI 53719, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Richmond
authors.affiliation: Nuclear Dynamics Programme, Babraham Institute, Cambridge, Cambridgeshire CB22 3AT, UK.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Spivakov
authors.affiliation: Roche NimbleGen, Incorporated, 500 South Rosa Road, Madison, WI 53719, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Burgess
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, 6525GA Nijmegen, the Netherlands. Electronic address: h.stunnenberg@ncmls.ru.nl.
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology; D005801:Genes, Homeobox; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011401:Promoter Regions, Genetic; D000072417:Protein Domains
chemical_list: D002843:Chromatin; D006657:Histones; D018398:Homeodomain Proteins; D003850:Deoxyribonuclease I