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
Lamina-associated domains: peripheral matters and internal affairs
TL;DR: Findings of lamin interactions with regulatory elements of active genes, and the role lamins may play in genome regulation are discussed, as well as the involvement of LADs in laminopathies.
Journal ArticleDOI
Looping Probabilities in Model Interphase Chromosomes
TL;DR: An extended theoretical and computational framework is provided to explain the currently available experimental data for various species on the basis of a unique, minimal model of decondensing chromosomes: a kinkable, topologically constraint, semiflexible polymer with the (FISH) Kuhn length of l(K) = 300 nm, 10 kinks per Mbp, and a contact distance of 45 nm.
Journal ArticleDOI
ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor.
Veit Scheble,Martin Braun,Rameen Beroukhim,Rameen Beroukhim,Craig H. Mermel,Craig H. Mermel,Christian Ruiz,Theresia Wilbertz,Ann-Cathrin Stiedl,Karen Petersen,Markus Reischl,Rainer Kuefer,David Schilling,Falko Fend,Glen Kristiansen,Matthew Meyerson,Matthew Meyerson,Mark A. Rubin,Lukas Bubendorf,Sven Perner +19 more
TL;DR: It is hypothesized that the ERG rearrangement as well as the distinct deletion site on 21q22.2–3 between TMPRSS2 and ERG are prostate-cancer-specific genomic alterations.
Journal ArticleDOI
Mechanisms of Interplay between Transcription Factors and the 3D Genome
TL;DR: This review summarizes the evidence for the diverse mechanisms by which TFs and their activity shape the 3D genome and vice versa and highlights outstanding questions and potential approaches for untangling the complex relation between TF activity and the3D genome.
Journal ArticleDOI
SRF Co-factors Control the Balance between Cell Proliferation and Contractility
Francesco Gualdrini,Cyril Esnault,Stuart Horswell,Aengus Stewart,Nik Matthews,Richard Treisman +5 more
TL;DR: It is shown that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation, and competition between TCFs and MRTFs for SRF determines the balance between antagonistic proliferative and contractile programs of gene expression.
References
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