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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Into the Wild: GWAS Exploration of Non-coding RNAs.
TL;DR: The upcoming of databases integrating single-nucleotide polymorphisms (SNPs) and non-coding RNAs together with novel technologies will hopefully facilitate the discovery of causal non-Coding variants associated to disease.
Journal ArticleDOI
Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments
Michael I. Robson,Jose I. de las Heras,Rafal Czapiewski,Aishwarya Sivakumar,Alastair R.W. Kerr,Eric C. Schirmer +5 more
TL;DR: Mapping LADs using Lamin B1-DamID during Jurkat T-cell activation found significant genome reorganization at the nuclear periphery dominated by release of loci frequently important for T- cell function, suggesting changes in LAD's during T-cells activation may provide an important additional mode of gene regulation.
Journal ArticleDOI
FAN-C: a feature-rich framework for the analysis and visualisation of chromosome conformation capture data
TL;DR: FAN-C, an easy-to-use command-line tool and powerful Python API with a broad feature set covering matrix generation, analysis, and visualisation for C-like data, can be used in combination with a large number of existing analysis tools, thus greatly simplifying Hi-C matrix analysis.
Journal ArticleDOI
Tracking microbial evolution in the human gut using Hi-C reveals extensive horizontal gene transfer, persistence and adaptation.
TL;DR: High-throughput chromosomal conformation capture identified changes in the gut microbiome over 10 years, including substantial exchange of accessory elements and adaptive evolution in core genomes.
Journal ArticleDOI
Inferential modeling of 3D chromatin structure
Siyu Wang,Jinbo Xu,Jianyang Zeng +2 more
TL;DR: A new Bayesian framework to derive the 3D architecture of a chromosome from 3C-based data is developed and an expectation-maximization (EM) based algorithm is proposed to estimate the unknown parameters of the Bayesian model and infer an ensemble of chromatin structures based on interaction frequency data.
References
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Book
The Fractal Geometry of Nature
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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
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TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
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