Comprehensive mapping of long-range interactions reveals folding principles of the human genome
Program in Gene Function and Expression; Department of Biochemistry and Molecular Pharmacology
Biotin; 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
Genetics and Genomics
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.
DOI of Published Version
Science. 2009 Oct 9;326(5950):289-93. Link to article on publisher's site
Science (New York, N.Y.)
Lieberman-Aiden, Erez; van Berkum, Nynke L.; Williams, Louise; Imakaev, Maxim; Ragoczy, Tobias; Telling, Agnes; Amit, Ido; Lajoie, Bryan R.; Sabo, Peter J.; Dorschner, Michael O.; Sandstrom, Richard; Berstein, Bradley; Bender, M. A.; Groudine, Mark; Gnirke, Andreas; Stamatoyannopoulos, John A.; Mirny, Leonid A.; Lander, Eric S.; and Dekker, Job, "Comprehensive mapping of long-range interactions reveals folding principles of the human genome" (2009). Program in Gene Function and Expression Publications and Presentations. 69.