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
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Journal ArticleDOI
Three-Dimensional Folding and Functional Organization Principles of the Drosophila Genome
Tom Sexton,Eitan Yaffe,Ephraim Kenigsberg,Frédéric Bantignies,Benjamin Leblanc,Michael Hoichman,Hugues Parrinello,Amos Tanay,Giacomo Cavalli +8 more
TL;DR: A high-resolution chromosomal contact map derived from a modified genome-wide chromosome conformation capture approach applied to Drosophila embryonic nuclei is presented, laying the foundation for detailed studies of chromosome structure and function in a genetically tractable system.
Journal ArticleDOI
Transcription factors: from enhancer binding to developmental control.
TL;DR: Current knowledge of transcription factor function from genomic and genetic studies is reviewed and how different strategies, including extensive cooperative regulation, progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development are discussed.
Journal ArticleDOI
Single-cell chromatin accessibility reveals principles of regulatory variation
Jason D. Buenrostro,Beijing Wu,Ulrike M. Litzenburger,David Ruff,Michael L. Gonzales,Michael Snyder,Howard Y. Chang,William J. Greenleaf +7 more
TL;DR: A robust method for mapping the accessible genome of individual cells by assay for transposase-accessible chromatin using sequencing (ATAC-seq) integrated into a programmable microfluidics platform is developed and single-cell analysis of DNA accessibility provides new insight into cellular variation of the ‘regulome’.
Journal ArticleDOI
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
Darío G. Lupiáñez,Darío G. Lupiáñez,Katerina Kraft,Katerina Kraft,Verena Heinrich,Peter Krawitz,Peter Krawitz,Francesco Brancati,Eva Klopocki,Denise Horn,Hülya Kayserili,John M. Opitz,Renata Laxova,Fernando Santos-Simarro,Fernando Santos-Simarro,Brigitte Gilbert-Dussardier,Lars Wittler,Marina Borschiwer,Stefan A. Haas,Marco Osterwalder,Martin Franke,Martin Franke,Bernd Timmermann,Jochen Hecht,Jochen Hecht,Malte Spielmann,Malte Spielmann,Axel Visel,Axel Visel,Axel Visel,Stefan Mundlos,Stefan Mundlos +31 more
TL;DR: The results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome.
Journal ArticleDOI
Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments
Neva C. Durand,Muhammad S. Shamim,Muhammad S. Shamim,Ido Machol,Ido Machol,Suhas S.P. Rao,Miriam H. Huntley,Eric S. Lander,Eric S. Lander,Erez Lieberman Aiden +9 more
TL;DR: Juicer as mentioned in this paper is an open-source tool for analyzing terabase-scale Hi-C datasets, which allows users without a computational background to transform raw sequence data into normalized contact maps with one click.
References
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