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

被引：5756

作者：

Lieberman-Aiden, Erez ^{[1
,2
,3
,4
]}

van Berkum, Nynke L. ^{[5
,6
]}

Williams, Louise ^{[1
]}

Imakaev, Maxim ^{[2
]}

Ragoczy, Tobias ^{[7
,8
]}

Telling, Agnes ^{[7
,8
]}

Amit, Ido ^{[1
]}

Lajoie, Bryan R. ^{[5
,6
]}

Sabo, Peter J. ^{[9
]}

Dorschner, Michael O. ^{[9
]}

Sandstrom, Richard ^{[9
]}

Bernstein, Bradley ^{[1
,10
]}

Bender, M. A. ^{[11
]}

Groudine, Mark ^{[7
,8
]}

Gnirke, Andreas ^{[1
]}

Stamatoyannopoulos, John ^{[9
]}

Mirny, Leonid A. ^{[2
,12
]}

Lander, Eric S. ^{[1
,13
,14
]}

Dekker, Job ^{[5
,6
]}

机构：

[1] Broad Inst Harvard, Cambridge, MA 02139 USA

[2] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[3] Harvard Univ, Dept Math, Dept Organism & Evolutionary Biol, Program Evolutionary Dynam, Cambridge, MA 02138 USA

[4] Harvard Univ, Dept Appl Math, Cambridge, MA 02138 USA

[5] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA

[6] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA

[7] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

[8] Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98195 USA

[9] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[10] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[11] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

[12] MIT, Dept Phys, Cambridge, MA 02139 USA

[13] MIT, Dept Biol, Cambridge, MA 02139 USA

[14] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

SCIENCE | 2009年 / 326卷 / 5950期

关键词：

GENE-REGULATION; IN-VIVO; CHROMOSOME CONFORMATION; NUCLEAR-ORGANIZATION; CHROMATIN ENVIRONMENT; INTERPHASE NUCLEUS; DNA; PROTEIN; CELLS; ARCHITECTURE;

D O I：

10.1126/science.1181369

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：289 / 293

页数：5

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