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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3D imaging of Sox2 enhancer clusters in embryonic stem cells
Zhe Liu,Wesley R. Legant,Bi-Chang Chen,Li M. Li,Jonathan B. Grimm,Luke D. Lavis,Eric Betzig,Robert Tjian,Robert Tjian +8 more
TL;DR: An integrated model linking cis-element 3D spatial distribution to local-versus-global target search modalities essential for regulating eukaryotic gene transcription is suggested.
Journal ArticleDOI
Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture
Alexandra Despang,Alexandra Despang,Robert Schöpflin,Robert Schöpflin,Martin Franke,Martin Franke,Salaheddine Ali,Salaheddine Ali,Ivana Jerković,Ivana Jerković,Ivana Jerković,Christina Paliou,Christina Paliou,Wing Lee Chan,Bernd Timmermann,Lars Wittler,Martin Vingron,Stefan Mundlos,Stefan Mundlos,Daniel M. Ibrahim,Daniel M. Ibrahim +20 more
TL;DR: It is shown that the removal of all major CTCF sites at the boundary and within the TAD resulted in a fusion of neighboring TADs, without major effects on gene expression, and TAD structures provide robustness and precision but are not essential for developmental gene regulation.
Journal ArticleDOI
Exploring long-range genome interactions using the WashU Epigenome Browser.
Xin Zhou,Rebecca F. Lowdon,Daofeng Li,Heather A. Lawson,Pamela A. F. Madden,Joseph F. Costello,Ting Wang +6 more
TL;DR: The WashU Epigenome Browser is extended, which currently hosts thousands of epigenome and transcriptome data sets for multiple cell types, tissues, individuals and species, to support multiple types of long-range genome interaction data, consistent with the hypothesis that chromatin domains are stable across cell types but can have different epigenetic profiles in different cells.
Journal ArticleDOI
Machine Learning for Integrating Data in Biology and Medicine: Principles, Practice, and Opportunities.
Marinka Zitnik,Francis Nguyen,Francis Nguyen,Bo Wang,Jure Leskovec,Anna Goldenberg,Michael M. Hoffman +6 more
TL;DR: In this paper, the authors describe the principles of data integration and discuss current methods and available implementations, as well as current challenges in biomedical integrative methods and their perspective on the future development of the field.
Journal ArticleDOI
Gene retention, fractionation and subgenome differences in polyploid plants.
TL;DR: This Review concludes that some mechanisms operate immediately at the wide-hybrid, and other mechanisms begin their operations later, and direct interaction of new paralogous genes, as measured using high-resolution chromatin conformation capture, should inform future research.
References
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