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
More filters
Journal ArticleDOI
Transcriptional gene network inference from a massive dataset elucidates transcriptome organization and gene function
Vincenzo Belcastro,Velia Siciliano,Francesco Gregoretti,Pratibha Mithbaokar,Gopuraja Dharmalingam,Stefania Berlingieri,Francesco Iorio,Gennaro Oliva,Roman S. Polishchuck,Nicola Brunetti-Pierri,Diego di Bernardo +10 more
TL;DR: It is shown that the network can be used to predict the biological function and subcellular localization of a protein, and to elucidate the function of a disease gene, and an online tool to explore the human and mouse gene networks is developed.
Journal ArticleDOI
Transcriptional Consequences of 16p11.2 Deletion and Duplication in Mouse Cortex and Multiplex Autism Families
Ian Blumenthal,Ashok Ragavendran,Serkan Erdin,Lambertus Klei,Aarathi Sugathan,Jolene R. Guide,Poornima Manavalan,Julian Q. Zhou,Vanessa C. Wheeler,Joshua Z. Levin,Carl Ernst,Kathryn Roeder,Bernie Devlin,James F. Gusella,James F. Gusella,Michael E. Talkowski,Michael E. Talkowski +16 more
TL;DR: It is suggested that through a combination of indirect regulatory effects and direct effects on nuclear architecture, alteration of 16p11.2 genes disrupts expression networks that involve other genes and pathways known to contribute to ASD, suggesting an overlap in mechanisms of pathogenesis.
Journal ArticleDOI
Multi -omics and metabolic modelling pipelines: challenges and tools for systems microbiology
Marco Fondi,Pietro Liò +1 more
TL;DR: Which layers of biological information are important for biotechnological and clinical purposes are discussed, with a special focus on bacterial metabolism and modelling procedures, and a general review of the most recent computational tools for performing large-scale datasets integration.
Journal ArticleDOI
FISH-ing for captured contacts: towards reconciling FISH and 3C
Geoffrey Fudenberg,Maxim Imakaev +1 more
TL;DR: It is demonstrated that contact frequency is distinct from average spatial distance, both in polymer simulations and in experimental data, which indicates that cross-validation of Hi-C and FISH should be carefully designed and that jointly considering contact frequency and spatial distance is crucial for fully understanding chromosome organization.
Journal ArticleDOI
Comparison of the three-dimensional organization of sperm and fibroblast genomes using the Hi-C approach
Nariman Battulin,Nariman Battulin,Veniamin S. Fishman,Veniamin S. Fishman,Alexander M. Mazur,Alexander M. Mazur,Mikhail Pomaznoy,A.A. Khabarova,Dmitry A. Afonnikov,Dmitry A. Afonnikov,Egor Prokhortchouk,Egor Prokhortchouk,Egor Prokhortchouk,Oleg L. Serov,Oleg L. Serov +14 more
TL;DR: The three-dimensional structure of the genome is passed through generations without being dramatically changed in sperm cells, and the dependence of the contact probability on genomic distance for sperm is close to the dependence predicted for the fractal globular folding of chromatin.
References
More filters
Book
The Fractal Geometry of Nature
TL;DR: This book is a blend of erudition, popularization, and exposition, and the illustrations include many superb examples of computer graphics that are works of art in their own right.
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
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Tarjei S. Mikkelsen,Manching Ku,Manching Ku,David B. Jaffe,Biju Issac,Biju Issac,Erez Lieberman Aiden,Erez Lieberman Aiden,Georgia Giannoukos,Pablo Alvarez,William Brockman,Tae Kyung Kim,Richard Koche,Richard Koche,Richard Koche,William Lee,Eric M. Mendenhall,Eric M. Mendenhall,Aisling O'Donovan,Aviva Presser,Carsten Russ,Xiaohui Xie,Alexander Meissner,Marius Wernig,Rudolf Jaenisch,Chad Nusbaum,Eric S. Lander,Eric S. Lander,Bradley E. Bernstein,Bradley E. Bernstein +29 more
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.
Journal ArticleDOI
Capturing Chromosome Conformation
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.
Related Papers (5)
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Elphège P. Nora,Bryan R. Lajoie,Edda G. Schulz,Luca Giorgetti,Luca Giorgetti,Luca Giorgetti,Ikuhiro Okamoto,Ikuhiro Okamoto,Ikuhiro Okamoto,Nicolas Servant,Nicolas Servant,Nicolas Servant,Tristan Piolot,Tristan Piolot,Tristan Piolot,Nynke L. van Berkum,Johannes Meisig,John W. Sedat,Joost Gribnau,Emmanuel Barillot,Emmanuel Barillot,Emmanuel Barillot,Nils Blüthgen,Job Dekker,Edith Heard,Edith Heard,Edith Heard +26 more