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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Dosage compensation in Drosophila melanogaster : epigenetic fine-tuning of chromosome-wide transcription
Thomas Conrad,Asifa Akhtar +1 more
TL;DR: This Review highlights the known facts and open questions of dosage compensation in D. melanogaster and investigates the intriguing interplay between multiple levels of local and long-range chromatin regulation required for the fine-tuned transcriptional activation of a heterogeneous gene population.
Journal ArticleDOI
DNA double-strand–break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice
Agnes Schipler,George Iliakis +1 more
TL;DR: It is suggested that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis.
Journal ArticleDOI
Capturing the essence of folding and functions of biomolecules using coarse-grained models
Changbong Hyeon,D. Thirumalai +1 more
TL;DR: Simulations using coarse-grained models to study folding of DNA, RNA and proteins and their variants are poised to address a wide range of problems in biology.
Journal ArticleDOI
Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation
Hideki Tanizawa,Osamu Iwasaki,Atsunari Tanaka,Joseph R. Capizzi,Priyankara Wickramasinghe,Mihee Lee,Zhiyan Fu,Ken-ichi Noma +7 more
TL;DR: The study suggests the presence of a global genome organization in fission yeast that is functionally similar to the recently proposed mammalian transcription factory.
Journal ArticleDOI
Distinct Epigenomic Features in End-Stage Failing Human Hearts
Mehregan Movassagh,Mun-Kit Choy,David A. Knowles,Lina Cordeddu,Syed Haider,Thomas A. Down,Lee Siggens,Ana Vujic,Ilenia Simeoni,Christopher J. Penkett,Martin Goddard,Pietro Liò,Martin R. Bennett,Roger Foo +13 more
TL;DR: The epigenome may control the expression of local or distal genes with critical functions in myocardial stress response and if epigenomic patterns track with disease progression, assays for the methylation scores may be useful for assessing prognosis in heart failure.
References
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