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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Journal ArticleDOI
Chromatin Replication and Epigenome Maintenance
Constance Alabert,Anja Groth +1 more
TL;DR: In this paper, the authors discuss the importance of chromatin structure and organization in eukaryotic genomes and their importance in maintaining the integrity of both genome and epigenome integrity with severe consequences for the organism.
Journal ArticleDOI
The 4D nucleome project
Job Dekker,Andrew S. Belmont,Mitchell Guttman,Victor O. Leshyk,John T. Lis,Stavros Lomvardas,Leonid A. Mirny,Clodagh C. O’Shea,Peter J. Park,Bing Ren,Joan C. Ritland Politz,Jay Shendure,Sheng Zhong +12 more
TL;DR: The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions.
Journal ArticleDOI
Systematic mapping of functional enhancer-promoter connections with CRISPR interference
Charles P. Fulco,Charles P. Fulco,Mathias Munschauer,Rockwell Anyoha,Glen Munson,Sharon R. Grossman,Sharon R. Grossman,Elizabeth M. Perez,Michael Kane,Brian Cleary,Brian Cleary,Eric S. Lander,Eric S. Lander,Eric S. Lander,Jesse M. Engreitz +14 more
TL;DR: A high-throughput approach that uses clustered regularly interspaced short palindromic repeats (CRISPRi) interference to discover regulatory elements and identify their target genes and can be applied to dissect transcriptional networks and interpret the contributions of noncoding genetic variation to human disease.
Journal ArticleDOI
Chromatin replication and epigenome maintenance
Constance Alabert,Anja Groth +1 more
TL;DR: Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization, and if DNA synthesis is perturbed, cells can suffer loss of both genome and epigenome integrity with severe consequences for the organism.
Journal ArticleDOI
Chromosome conformation elucidates regulatory relationships in developing human brain
Hyejung Won,Luis de la Torre-Ubieta,Jason L. Stein,Neelroop N. Parikshak,Jerry Huang,Carli K. Opland,Michael J. Gandal,Gavin J. Sutton,Farhad Hormozdiari,Daning Lu,Changhoon Lee,Eleazar Eskin,Irina Voineagu,Jason Ernst,Daniel H. Geschwind +14 more
TL;DR: High-resolution 3D maps of chromatin contacts during human corticogenesis are generated, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease.
References
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