Comprehensive mapping of long-range interactions reveals folding principles of the human genome.
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.
Lieberman-Aiden
Erez
E
Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), MA 02139, USA.
van Berkum
Nynke L
NL
Williams
Louise
L
Imakaev
Maxim
M
Ragoczy
Tobias
T
Telling
Agnes
A
Amit
Ido
I
Lajoie
Bryan R
BR
Sabo
Peter J
PJ
Dorschner
Michael O
MO
Sandstrom
Richard
R
Bernstein
Bradley
B
Bender
M A
MA
Groudine
Mark
M
Gnirke
Andreas
A
Stamatoyannopoulos
John
J
Mirny
Leonid A
LA
Lander
Eric S
ES
Dekker
Job
J
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
D002843:Chromatin; D001710:Biotin; D004247:DNA