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
Genomics of long-range regulatory elements.
TL;DR: The advantages and limitations of sequence conservation as a predictor of regulatory function are discussed and complementary emerging technologies now being applied to annotate regulatory elements in vertebrate genomes are presented.
Journal ArticleDOI
The liquid nucleome - phase transitions in the nucleus at a glance.
TL;DR: How membrane-less compartments in the nucleus are formed by phase separation and help to organize and regulate nuclear functions is discussed.
Journal ArticleDOI
Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes
Yinxiu Zhan,Yinxiu Zhan,Luca Mariani,Iros Barozzi,Edda G. Schulz,Nils Blüthgen,Nils Blüthgen,Michael B. Stadler,Michael B. Stadler,Guido Tiana,Luca Giorgetti +10 more
TL;DR: A novel algorithm named CaTCH is presented that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation, which is a single and biologically relevant parameter and shows that previously reported folding layers appear at different insulation levels.
Journal ArticleDOI
Microscopy-Based Chromosome Conformation Capture Enables Simultaneous Visualization of Genome Organization and Transcription in Intact Organisms
Andrés M. Cardozo Gizzi,Diego I. Cattoni,Jean-Bernard Fiche,Sergio Martín Espínola,Julian Gurgo,Olivier Messina,Christophe Houbron,Yuki Ogiyama,Giorgio L. Papadopoulos,Giacomo Cavalli,Mounia Lagha,Marcelo Nollmann +11 more
TL;DR: The ability of Hi-M to explore the multi-scale chromosome architecture with spatial resolution at different stages of development or during the cell cycle will be key to understanding the mechanisms and consequences of the 4D organization of the genome.
Journal ArticleDOI
Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains
TL;DR: A fitting-free, minimal model: bivalent or multivalent red and green ‘transcription factors’ bind to cognate sites in strings of beads to form molecular bridges stabilizing loops that proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales.
References
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