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.