title: Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments.
abstract: Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity.
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Wijchers
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Peter H L
authors.initials: PHL
authors.lastname: Krijger
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Geeven
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Annette
authors.initials: A
authors.lastname: Denker
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Marjon J A M
authors.initials: MJAM
authors.lastname: Verstegen
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Valdes-Quezada
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vermeulen
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Janssen
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Teunissen
authors.affiliation: Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, the Netherlands.
authors.forename: Lisette C M
authors.initials: LCM
authors.lastname: Anink-Groenen
authors.affiliation: Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, the Netherlands.
authors.forename: Pernette J
authors.initials: PJ
authors.lastname: Verschure
authors.affiliation: Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Electronic address: w.delaat@hubrecht.eu.
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D020090:Chromosome Segregation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005786:Gene Expression Regulation; D056426:Genetic Loci; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon; D056968:Lac Repressors / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D000071317:Nanog Homeobox Protein; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D056968:Lac Repressors; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2
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