title: 3D structures of individual mammalian genomes studied by single-cell Hi-C.
abstract: The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell. By contrast, A and B compartments, lamina-associated domains and active enhancers and promoters are organized in a consistent way on a genome-wide basis in every cell, suggesting that they could drive chromosome and genome folding. By studying genes regulated by pluripotency factor and nucleosome remodelling deacetylase (NuRD), we illustrate how the determination of single-cell genome structure provides a new approach for investigating biological processes.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.|MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Stevens
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Lando
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Srinjan
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Liam P
authors.initials: LP
authors.lastname: Atkinson
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Lee
authors.affiliation: Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Leeb
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Kai J
authors.initials: KJ
authors.lastname: Wohlfahrt
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Wayne
authors.initials: W
authors.lastname: Boucher
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.|Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: Aoife
authors.initials: A
authors.lastname: O'Shaughnessy-Kirwan
authors.affiliation: Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Cramard
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Faure
authors.affiliation: Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: Meryem
authors.initials: M
authors.lastname: Ralser
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Blanco
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Morey
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Sansó
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Matthieu G S
authors.initials: MGS
authors.lastname: Palayret
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.|Universitat Pompeu Fabra, 08003 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: Ben
authors.initials: B
authors.lastname: Lehner
authors.affiliation: EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.|Universitat Pompeu Fabra, 08003 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
authors.affiliation: Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: Anton
authors.initials: A
authors.lastname: Wutz
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.|Wellcome Trust - MRC Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Hendrich
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Dave
authors.initials: D
authors.lastname: Klenerman
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
authors.forename: Ernest D
authors.initials: ED
authors.lastname: Laue
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D016193:G1 Phase; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016678:Genome / Q000235:genetics; D006238:Haploidy; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D057054:Molecular Imaging / Q000379:methods* / Q000592:standards; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D059010:Single-Cell Analysis / Q000379:methods* / Q000592:standards; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009707:Nucleosomes; D012097:Repressor Proteins; D000097722:Cohesins; C000619698:Ctcf protein, mouse