A high-resolution map of the three-dimensional chromatin interactome in human cells
Fulai Jin,Yan Li,Jesse R. Dixon,Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Zhen Ye,Ah Young Lee,Chia-An Yen,Anthony D. Schmitt,Anthony D. Schmitt,Celso A. Espinoza,Bing Ren,Bing Ren +13 more
TLDR
A comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C) is reported and suggests that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection of target genes by a ubiquitous transcription activator in a cell-specific manner.Abstract:
A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.read more
Citations
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Journal ArticleDOI
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Suhas S.P. Rao,Miriam H. Huntley,Neva C. Durand,Elena K. Stamenova,Ivan D. Bochkov,James T. Robinson,James T. Robinson,Adrian L. Sanborn,Ido Machol,Ido Machol,Arina D. Omer,Arina D. Omer,Eric S. Lander,Eric S. Lander,Eric S. Lander,Erez Lieberman Aiden +15 more
TL;DR: In situ Hi-C is used to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types, identifying ∼10,000 loops that frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.
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
HiC-Pro: an optimized and flexible pipeline for Hi-C data processing
Nicolas Servant,Nelle Varoquaux,Nelle Varoquaux,Nelle Varoquaux,Bryan R. Lajoie,Eric Viara,Chong-Jian Chen,Jean-Philippe Vert,Jean-Philippe Vert,Jean-Philippe Vert,Edith Heard,Edith Heard,Edith Heard,Job Dekker,Emmanuel Barillot,Emmanuel Barillot,Emmanuel Barillot +16 more
TL;DR: This work applied HiC-Pro to different Hi-C datasets, demonstrating its ability to easily process large data in a reasonable time and its fast implementation of the iterative correction method.
Journal ArticleDOI
Three-dimensional Epigenome Statistical Model: Genome-wide Chromatin Looping Prediction.
TL;DR: The 3DEpiLoop algorithm predicts three-dimensional chromatin looping interactions within topologically associating domains (TADs) from one-dimensional epigenomics and transcription factor profiles using the statistical learning.
Journal ArticleDOI
Transcriptional enhancers: from properties to genome-wide predictions.
TL;DR: How properties of enhancer sequences and chromatin are used to predict enhancers in genome-wide studies are discussed and recently developed high-throughput methods that allow the direct testing and identification of enhancers on the basis of their activity are covered.
References
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An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities
Sven Heinz,Christopher Benner,Nathanael J. Spann,Eric Bertolino,Yin C. Lin,Peter Laslo,Jason X. Cheng,Cornelis Murre,Harinder Singh,Harinder Singh,Christopher K. Glass +10 more
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Journal Article
An integrated encyclopedia of DNA elements in the human genome.
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
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
TL;DR: 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.
Journal ArticleDOI
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Feng Yue,Audrey Kim,Yan-Yan Li,Yin-Zhong Shen,Ming Hu,Jun Liu,Bing Ren,Bing Ren +10 more
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
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