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
Chromosome Conformation Capture and Beyond: Toward an Integrative View of Chromosome Structure and Function.
TL;DR: A review of chromosome conformation capture methods can be found in this paper, focusing on the contribution of complementary methodologies to our understanding of structures revealed by 3C methods and their biological implications and discuss the next technical and conceptual frontiers.
Journal ArticleDOI
Identifying cis Elements for Spatiotemporal Control of Mammalian DNA Replication
Jiao Sima,Abhijit Chakraborty,Vishnu Dileep,Marco Michalski,Kyle N. Klein,Nicolas P. Holcomb,Jesse L. Turner,Michelle T. Paulsen,Juan Carlos Rivera-Mulia,Claudia Trevilla-Garcia,Daniel A. Bartlett,Peiyao A. Zhao,Brian K. Washburn,Elphège P. Nora,Katerina Kraft,Katerina Kraft,Stefan Mundlos,Stefan Mundlos,Benoit G. Bruneau,Mats Ljungman,Peter Fraser,Peter Fraser,Ferhat Ay,Ferhat Ay,David M. Gilbert +24 more
TL;DR: It is demonstrated that discrete cis-regulatory elements orchestrate domain-wide RT, A/B compartmentalization, TAD architecture, and transcription, revealing fundamental principles linking genome structure and function.
Journal ArticleDOI
Functional Nuclear Organization of Transcription and DNA Replication A Topographical Marriage between Chromatin Domains and the Interchromatin Compartment
Yolanda Markaki,Manuel Gunkel,Lothar Schermelleh,S. Beichmanis,Jürgen Neumann,M. Heidemann,Heinrich Leonhardt,Dirk Eick,Christoph Cremer,Thomas Cremer +9 more
TL;DR: The nuclear topography of RNA transcription and DNA replication in mammalian cell types is studied with super-resolution fluorescence microscopy, which offers a resolution beyond the classical Abbe/Raleigh limit and confirms the presence of RNA Pol II clusters indicative of transcription factories.
Journal ArticleDOI
Constructing 3D interaction maps from 1D epigenomes
Yun Zhu,Zhao Chen,Kai Zhang,Mengchi Wang,David Medovoy,John W. Whitaker,Bo Ding,Nan Li,Lina Zheng,Wei Wang +9 more
TL;DR: EpiTensor, an algorithm to identify 3D spatial associations within topologically associating domains (TADs) from 1D maps of histone modifications, chromatin accessibility and RNA-seq, is presented and it is demonstrated that active promoter–promoter, promoter–enhancer and enhancer-enhancer associations identified by EpiT sensor are highly concordant with those detected by Hi-C, ChIA-PET and eQTL analyses at 200 bp resolution
Journal ArticleDOI
Chromosome positioning from activity-based segregation
TL;DR: The computer simulations indicate that gene density-dependent radial segregation of chromosomes arises as a robust consequence of differences in non-equilibrium activity across chromosomes, and it is shown that a variety of non-random positional distributions emerge through the interplay of such activity, nuclear shape and specific interactions of chromosomes with the nuclear envelope.
References
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