title: Comprehensive mapping of long-range interactions reveals folding principles of the human genome.
abstract: We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), MA 02139, USA.
authors.forename: Erez
authors.initials: E
authors.lastname: Lieberman-Aiden
authors.forename: Nynke L
authors.initials: NL
authors.lastname: van Berkum
authors.forename: Louise
authors.initials: L
authors.lastname: Williams
authors.forename: Maxim
authors.initials: M
authors.lastname: Imakaev
authors.forename: Tobias
authors.initials: T
authors.lastname: Ragoczy
authors.forename: Agnes
authors.initials: A
authors.lastname: Telling
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Lajoie
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sabo
authors.forename: Michael O
authors.initials: MO
authors.lastname: Dorschner
authors.forename: Richard
authors.initials: R
authors.lastname: Sandstrom
authors.forename: Bradley
authors.initials: B
authors.lastname: Bernstein
authors.forename: M A
authors.initials: MA
authors.lastname: Bender
authors.forename: Mark
authors.initials: M
authors.lastname: Groudine
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.forename: John
authors.initials: J
authors.lastname: Stamatoyannopoulos
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Mirny
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Job
authors.initials: J
authors.lastname: Dekker
mesh_terms: D001710:Biotin; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000648:ultrastructure*; D002843:Chromatin / Q000737:chemistry*; D047369:Chromatin Immunoprecipitation; D002877:Chromosomes, Human / Q000737:chemistry / Q000648:ultrastructure; D019295:Computational Biology; D004247:DNA / Q000737:chemistry*; D015723:Gene Library; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008958:Models, Molecular; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D025341:Principal Component Analysis; D011487:Protein Conformation; D017422:Sequence Analysis, DNA
chemical_list: D002843:Chromatin; D001710:Biotin; D004247:DNA