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Science DOI:10.1126/science.1181369

Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

Publication TypeJournal Article
Year of Publication2009
AuthorsLieberman-Aiden, E, van Berkum, NL, Williams, L, Imakaev, M, Ragoczy, T, Telling, A, Amit, I, Lajoie, BR, Sabo, PJ, Dorschner, MO, Sandstrom, R, Bernstein, B, Bender, MA, Groudine, M, Gnirke, A, Stamatoyannopoulos, J, Mirny, LA, Lander, ES, Dekker, J
Date Published2009 Oct 09
KeywordsBiotin, Cell Line, Transformed, Cell Nucleus, Chromatin, Chromatin Immunoprecipitation, Chromosomes, Human, Computational Biology, DNA, Gene Library, Genome, Human, Humans, In Situ Hybridization, Fluorescence, Models, Molecular, Monte Carlo Method, Nucleic Acid Conformation, Principal Component Analysis, Protein Conformation, Sequence Analysis, DNA

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.


Alternate JournalScience
PubMed ID19815776
PubMed Central IDPMC2858594
Grant ListR37DK44746 / DK / NIDDK NIH HHS / United States
HG003143 / HG / NHGRI NIH HHS / United States
U54HG004592 / HG / NHGRI NIH HHS / United States
R01 HG003143 / HG / NHGRI NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
R37 DK044746 / DK / NIDDK NIH HHS / United States
R01HL06544 / HL / NHLBI NIH HHS / United States
U54 HG004592 / HG / NHGRI NIH HHS / United States
R01 HG003143-06 / HG / NHGRI NIH HHS / United States