Comprehensive Mapping of Long-range Interactions Reveals Folding Principles of the Human Genome

Overview

Journal Science

Specialty Science

Date 2009 Oct 10

PMID 19815776

Citations 4180

Authors

Erez Lieberman-Aiden

Nynke L van Berkum

Louise Williams

Maxim Imakaev

Tobias Ragoczy

Agnes Telling

Ido Amit

Bryan R Lajoie

Peter J Sabo

Michael O Dorschner

Richard Sandstrom

Bradley Bernstein

M A Bender

Mark Groudine

Andreas Gnirke

John Stamatoyannopoulos

Leonid A Mirny

Eric S Lander

Job Dekker

Affiliations

Soon will be listed here.

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.

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