title: Long-range chromatin contacts in embryonic stem cells reveal a role for pluripotency factors and polycomb proteins in genome organization.
abstract: The relationship between 3D organization of the genome and gene-regulatory networks is poorly understood. Here, we examined long-range chromatin interactions genome-wide in mouse embryonic stem cells (ESCs), iPSCs, and fibroblasts and uncovered a pluripotency-specific genome organization that is gradually reestablished during reprogramming. Our data confirm that long-range chromatin interactions are primarily associated with the spatial segregation of open and closed chromatin, defining overall chromosome conformation. Additionally, we identified two further levels of genome organization in ESCs characterized by colocalization of regions with high pluripotency factor occupancy and strong enrichment for Polycomb proteins/H3K27me3, respectively. Underlining the independence of these networks and their functional relevance for genome organization, loss of the Polycomb protein Eed diminishes interactions between Polycomb-regulated regions without altering overarching chromosome conformation. Together, our data highlight a pluripotency-specific genome organization in which pluripotency factors such as Nanog and H3K27me3 occupy distinct nuclear spaces and reveal a role for cell-type-specific gene-regulatory networks in genome organization.
authors.affiliation: Department of Biological Chemistry at the David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|University of California, Los Angeles, CA, 90095, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Denholtz
authors.affiliation: Department of Biological Chemistry at the David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|University of California, Los Angeles, CA, 90095, USA.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bonora
authors.affiliation: Department of Biological Chemistry at the David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|University of California, Los Angeles, CA, 90095, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Chronis
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center, Utrecht, 3584 CT, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Splinter
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center, Utrecht, 3584 CT, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.affiliation: Department of Biological Chemistry at the David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|University of California, Los Angeles, CA, 90095, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, Los Angeles, CA, 90095, USA.|University of California, Los Angeles, CA, 90095, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Department of Biological Chemistry at the David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|University of California, Los Angeles, CA, 90095, USA.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Plath
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002843:Chromatin; D006657:Histones; D063146:Polycomb-Group Proteins
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