title: The pluripotent genome in three dimensions is shaped around pluripotency factors.
abstract: It is becoming increasingly clear that the shape of the genome importantly influences transcription regulation. Pluripotent stem cells such as embryonic stem cells were recently shown to organize their chromosomes into topological domains that are largely invariant between cell types. Here we combine chromatin conformation capture technologies with chromatin factor binding data to demonstrate that inactive chromatin is unusually disorganized in pluripotent stem-cell nuclei. We show that gene promoters engage in contacts between topological domains in a largely tissue-independent manner, whereas enhancers have a more tissue-restricted interaction profile. Notably, genomic clusters of pluripotency factor binding sites find each other very efficiently, in a manner that is strictly pluripotent-stem-cell-specific, dependent on the presence of Oct4 and Nanog protein and inducible after artificial recruitment of Nanog to a selected chromosomal site. We conclude that pluripotent stem cells have a unique higher-order genome structure shaped by pluripotency factors. We speculate that this interactome enhances the robustness of the pluripotent state.
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Elzo
authors.initials: E
authors.lastname: de Wit
authors.forename: Britta A M
authors.initials: BA
authors.lastname: Bouwman
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Petra
authors.initials: P
authors.lastname: Klous
authors.forename: Erik
authors.initials: E
authors.lastname: Splinter
authors.forename: Marjon J A M
authors.initials: MJ
authors.lastname: Verstegen
authors.forename: Peter H L
authors.initials: PH
authors.lastname: Krijger
authors.forename: Nicola
authors.initials: N
authors.lastname: Festuccia
authors.forename: Elphège P
authors.initials: EP
authors.lastname: Nora
authors.forename: Maaike
authors.initials: M
authors.lastname: Welling
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
authors.forename: Niels
authors.initials: N
authors.lastname: Geijsen
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Poot
authors.forename: Ian
authors.initials: I
authors.lastname: Chambers
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D045584:Chromosome Positioning; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D016678:Genome / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D009928:Organ Specificity; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D055748:SOXB1 Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse