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
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Journal ArticleDOI
Regulation of the Human Telomerase Gene TERT by Telomere Position Effect-Over Long Distances (TPE-OLD): Implications for Aging and Cancer.
Wanil Kim,Andrew T. Ludlow,Jaewon Min,Jérôme D. Robin,Guido Stadler,Ilgen Mender,Tsung Po Lai,Ning Zhang,Woodring E. Wright,Jerry W. Shay +9 more
TL;DR: Substantial evidence is provided for a new regulatory control mechanism of the rate limiting catalytic protein component of telomerase (hTERT) that is determined by the length of telomeres and new insights are provided into how the changes in genome structure during replicative aging result in an increased susceptibility to age-related diseases and cancer prior to the initiation of a DNA damage signal.
Journal ArticleDOI
Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin interaction map
TL;DR: The results indicate that DNA looping is also associated with gene repression, and loops were frequently located within domains of PcG-repressed chromatin.
Journal ArticleDOI
Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells.
Hilmar Strickfaden,Thomas O. Tolsma,Ajit Sharma,D. Alan Underhill,Jeffrey C. Hansen,Michael J. Hendzel +5 more
TL;DR: The results reveal that condensed chromatin exists in a solid-like state whose properties resist external forces and create an elastic gel and provides a scaffold that supports liquid-liquid phase separation of chromatin binding proteins.
Journal ArticleDOI
Emerging roles of mechanical forces in chromatin regulation.
TL;DR: The mechanisms by which the nucleus, and chromatin in particular, respond to changes in the mechanical microenvironment of the cell, resulting in architectural and transcriptional alterations, and thereby facilitating cellular adaption are discussed.
Journal ArticleDOI
Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain
Maxence Vieux-Rochas,Pierre J. Fabre,Marion Leleu,Denis Duboule,Denis Duboule,Daan Noordermeer +5 more
TL;DR: A simplified view of nuclear organization is provided whereby Polycomb proteins may have evolved to repress genes located in gene-dense regions whose position is restricted to central, active, nuclear environments.
References
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The Fractal Geometry of Nature
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