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
Non-coding transcription instructs chromatin folding and compartmentalization to dictate enhancer-promoter communication and t cell fate
Takeshi Isoda,Amanda J. Moore,Zhaoren He,Vivek Chandra,Masatoshi Aida,Matthew Denholtz,Jan Piet van Hamburg,Kathleen M. Fisch,Aaron N. Chang,Shawn P. Fahl,David L. Wiest,Cornelis Murre +11 more
TL;DR: Large-scale changes in nuclear architecture were associated with the deposition of activating epigenetic marks across the loop domain, plausibly facilitating phase separation and indicating how, during developmental progression and tumor suppression, non-coding transcription orchestrates chromatin folding and compartmentalization to direct with high precision enhancer-promoter communication.
Journal ArticleDOI
Bayesian inference of spatial organizations of chromosomes.
Ming Hu,Ke Deng,Zhaohui S. Qin,Jesse R. Dixon,Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Jennifer S. Fang,Bing Ren,Bing Ren,Jun Liu +10 more
TL;DR: A novel Bayesian probabilistic approach is described, denoted as “Bayesian 3D constructor for Hi-C data” (BACH), to infer the consensus 3D chromosomal structure and a variant algorithm BACH-MIX is described to study the structural variations of chromatin in a cell population.
Journal ArticleDOI
RNA Polymerase II cluster dynamics predict mRNA output in living cells
Won-Ki Cho,Namrata Jayanth,Brian P. English,Takuma Inoue,J Owen Andrews,William Conway,Jonathan B. Grimm,Jan-Hendrik Spille,Luke D. Lavis,Timothée Lionnet,Ibrahim I Cisse +10 more
TL;DR: A live-cell super-resolution approach is developed to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus and suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output.
Journal ArticleDOI
The effects of chromatin organization on variation in mutation rates in the genome
TL;DR: Recent studies showing associations between chromatin state and mutation rates, including pairwise and multivariate investigations of germline and somatic mutations, indicate an intricate interplay between the nucleotide sequence of DNA and its dynamic packaging into chromatin, and have important implications for current biomedical research.
Book ChapterDOI
4C technology: protocols and data analysis.
Harmen J.G. van de Werken,Paula J P de Vree,Erik Splinter,Sjoerd J B Holwerda,Petra Klous,Elzo de Wit,Wouter de Laat +6 more
TL;DR: The design, application, and data analysis of 4C-seq experiments are discussed, and criteria to assess data quality and how different restriction enzymes and cross-linking conditions affect results are defined.
References
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Book
The Fractal Geometry of Nature
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
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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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TL;DR: Using the yeast Saccharomyces cerevisiae, this work could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis and found that chromatin is highly flexible throughout.
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