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

Publication Type:

Journal Article


Science (New York, N.Y.), Volume 326, Issue 5950, p.289-93 (2009)


2009, Basic Sciences Division, Biotin, Cell Line, Transformed, Cell Nucleus, Center-Authored Paper, chromatin, Chromatin Immunoprecipitation, Chromosomes, Human, Clinical Research Division, 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, Scientific Imaging Core Facility, Sequence Analysis, DNA, Shared Resources


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.