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

Science
Authors
Keywords
Abstract

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.

Year of Publication
2009
Journal
Science
Volume
326
Issue
5950
Pages
289-93
Date Published
2009 Oct 09
ISSN
1095-9203
URL
DOI
10.1126/science.1181369
PubMed ID
19815776
PubMed Central ID
PMC2858594
Links
Grant list
R37DK44746 / 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