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
Dynamics of gene silencing during X inactivation using allele-specific RNA-seq.
Hendrik Marks,Hindrik H. D. Kerstens,Tahsin Stefan Barakat,Erik Splinter,René A.M. Dirks,Guido van Mierlo,Onkar Joshi,Shuang-Yin Wang,Tomas Babak,Cornelis A. Albers,Tüzer Kalkan,Austin Smith,Alice Jouneau,Wouter de Laat,Joost Gribnau,Hendrik G. Stunnenberg +15 more
TL;DR: The gene silencing observed during XCI provides further insight in the establishment of the repressive complex formed by the inactive X chromosome, and the association of escape regions with TADs, in mouse and human, suggests that Tads are the primary targets during propagation of XCI over the X chromosome.
Journal ArticleDOI
Identification of significant chromatin contacts from HiChIP data by FitHiChIP.
Sourya Bhattacharyya,Vivek Chandra,Pandurangan Vijayanand,Pandurangan Vijayanand,Pandurangan Vijayanand,Ferhat Ay,Ferhat Ay +6 more
TL;DR: FitHiChIP is a computational method for loop calling from HiChIP/PLAC-seq data, which jointly models the non-uniform coverage and genomic distance scaling of contact counts to compute statistical significance estimates and develops a technique to filter putative bystander loops that can be explained by stronger adjacent loops.
Journal ArticleDOI
Systems biology in cardiovascular disease: a multiomics approach.
TL;DR: In this article, the authors describe the techniques and sources of omics data, outline network theory, and highlight exemplars of novel approaches that combine gene regulatory and co-expression networks, proteomics, metabolomics, lipidomics and phenomics with informatics techniques to provide new insights into cardiovascular disease.
Journal ArticleDOI
Bioinformatics and Drug Discovery.
TL;DR: The conceptual framework that drives the collection of high-throughput data is presented, the utility and potential of mining these data in drug discovery are summarized, a few inherent limitations in data and softwaremining these data are outlined, and news ways to refine analysis are pointed out.
Journal ArticleDOI
The nuclear envelope as a chromatin organizer.
TL;DR: This work reviews both what is known and what is speculated about the role of the nuclear envelope in genome organization, particularly with respect to the positioning and repositioning of genes and chromosomes within the nucleus during differentiation.
References
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