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,Tobias Ragoczy,Agnes Telling,Agnes Telling,Ido Amit,Bryan R. Lajoie,Peter J. Sabo,Michael O. Dorschner,Richard Sandstrom,Bradley E. Bernstein,Bradley E. Bernstein,Michaël Bender,Mark Groudine,Mark Groudine,Andreas Gnirke,John A. Stamatoyannopoulos,Leonid A. Mirny,Eric S. Lander,Eric S. Lander,Job Dekker +23 more
TLDR
Hi-C is described, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing and demonstrates the power of Hi-C to map the dynamic conformations of entire genomes.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.read more
Citations
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Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization.
TL;DR: The results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization and find that chromosomes are organized into multiple levels of interacting domains.
Journal ArticleDOI
Genome-wide analysis of local chromatin packing in Arabidopsis thaliana
Congmao Wang,Chang Liu,Damian Roqueiro,Dominik G. Grimm,Rebecca Schwab,Claude Becker,Christa Lanz,Detlef Weigel +7 more
TL;DR: It is found that local chromatin packing differs from the patterns seen in animals, with kilobasepair-sized segments that have much higher intrachromosome interaction rates than neighboring regions, representing a dominant local structural feature of genome conformation in A. thaliana.
Journal ArticleDOI
Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.
Emily M. Darrow,Miriam H. Huntley,Olga Dudchenko,Elena Stamenova,Neva C. Durand,Zhuo Sun,Su Chen Huang,Adrian L. Sanborn,Ido Machol,Muhammad S. Shamim,Andrew P. Seberg,Eric S. Lander,Brian P. Chadwick,Erez Lieberman Aiden +13 more
TL;DR: 3D mapping, microscopy, and genome editing are combined to study the structure of the inactive X chromosome, focusing on the role of DXZ4, and it is found that superloops and superdomains are conserved across humans, macaque, and mouse.
Journal ArticleDOI
TADs are 3D structural units of higher-order chromosome organization in Drosophila
Quentin Szabo,Daniel Jost,Jia-Ming Chang,Diego I. Cattoni,Giorgio L. Papadopoulos,Boyan B. Bonev,Tom Sexton,Julian Gurgo,Caroline Jacquier,Marcelo Nollmann,Frédéric Bantignies,Giacomo Cavalli +11 more
TL;DR: Results indicate that TADs are fundamental 3D genome units that engage in dynamic higher-order inter-TAD connections, likely to play a major role in regulatory transactions during DNA-dependent processes.
Journal ArticleDOI
High-resolution interrogation of functional elements in the noncoding genome
Neville E. Sanjana,Neville E. Sanjana,Jason Wright,Jason Wright,Kaijie Zheng,Kaijie Zheng,Ophir Shalem,Ophir Shalem,Pierre Fontanillas,Julia Joung,Julia Joung,Christine S. Cheng,Christine S. Cheng,Aviv Regev,Aviv Regev,Feng Zhang,Feng Zhang +16 more
TL;DR: A CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases surrounding the genes NF1, NF2, and CUL3, which are involved in BRAF inhibitor resistance in melanoma, finds that noncoding locations that modulate drug resistance also harbor predictive hallmarks ofnoncoding function.
References
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