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

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

doi:10.1126/science.1181369

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

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

Research output: Contribution to journal › Article › peer-review

6100 Citations (Scopus)

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.

Original language	English
Pages (from-to)	289-293
Number of pages	5
Journal	Science
Volume	326
Issue number	5950
DOIs	https://doi.org/10.1126/science.1181369
Publication status	Published - 9 Oct 2009
Externally published	Yes

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Lieberman-Aiden, E., Van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., Sandstrom, R., Bernstein, B., Bender, M. A., Groudine, M., Gnirke, A., Stamatoyannopoulos, J., Mirny, L. A., Lander, E. S., & Dekker, J. (2009). Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science, 326(5950), 289-293. https://doi.org/10.1126/science.1181369

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title = "Comprehensive mapping of long-range interactions reveals folding principles of the human genome",

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.",

author = "Erez Lieberman-Aiden and {Van Berkum}, {Nynke L.} and Louise Williams and Maxim Imakaev and Tobias Ragoczy and Agnes Telling and Ido Amit and Lajoie, {Bryan R.} and Sabo, {Peter J.} and Dorschner, {Michael O.} and Richard Sandstrom and Bradley Bernstein and Bender, {M. A.} and Mark Groudine and Andreas Gnirke and John Stamatoyannopoulos and Mirny, {Leonid A.} and Lander, {Eric S.} and Job Dekker",

year = "2009",

month = oct,

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doi = "10.1126/science.1181369",

language = "English",

volume = "326",

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Lieberman-Aiden, E, Van Berkum, NL, Williams, L, Imakaev, M, Ragoczy, T, Telling, A, Amit, I, Lajoie, BR, Sabo, PJ, Dorschner, MO, Sandstrom, R, Bernstein, B, Bender, MA, Groudine, M, Gnirke, A, Stamatoyannopoulos, J, Mirny, LA, Lander, ES & Dekker, J 2009, 'Comprehensive mapping of long-range interactions reveals folding principles of the human genome', Science, vol. 326, no. 5950, pp. 289-293. https://doi.org/10.1126/science.1181369

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T1 - Comprehensive mapping of long-range interactions reveals folding principles of the human genome

AU - Lieberman-Aiden, Erez

AU - Van Berkum, Nynke L.

AU - Williams, Louise

AU - Imakaev, Maxim

AU - Ragoczy, Tobias

AU - Telling, Agnes

AU - Amit, Ido

AU - Lajoie, Bryan R.

AU - Sabo, Peter J.

AU - Dorschner, Michael O.

AU - Sandstrom, Richard

AU - Bernstein, Bradley

AU - Bender, M. A.

AU - Groudine, Mark

AU - Gnirke, Andreas

AU - Stamatoyannopoulos, John

AU - Mirny, Leonid A.

AU - Lander, Eric S.

AU - Dekker, Job

PY - 2009/10/9

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AB - 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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JF - Science

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

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