A high-resolution map of three-dimensional chromatin interactome in human cells

By Fulai Jin, Yan Li, Jesse R. Dixon, Siddarth Selvaraj, Z. Ye, Ahyoung Lee, C. Yen, Anthony D. Schmitt, Celso A. Espinoza, Bing Ren. Nature, 2013

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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.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/06a2b47f5789f59d21974edfef0c22b05bd27131

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Citations in the corpus

High-Throughput Sequencing Technologies (2015, neutral): “Strikingly, fewer than 10,000 looping events were observed genome wide, which is far smaller than previous estimates (Jin et al., 2013).”
HiCRep: assessing the reproducibility of Hi-C data using a stratum-adjusted correlation coefficient (2017, neutral): “…investigators often rely on either visual inspection of the Hi-C interaction heatmap or examination of the ratio of long-range interaction read pairs over the total sequenced reads (Dixon et al. 2012, 2015; Jin et al. 2013), but neither of these approaches is supported by robust statistics.”
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions (2015, background): “While the present study focused on one locus and one set of related morphological phenotypes, TAD data for the entire human and mouse genome are becoming available at increasing resolution (Jin et al., 2013; Rao et al., 2014).”
PEDLA: predicting enhancers with a deep learning-based algorithmic framework (2016, background): “In higher eukaryotes, enhancers recruit transcription factors (TFs) and cofactors to orchestrate vital biological processes including development and differentiation (5,6), maintenance of cell identity (7-9), response to stimuli (10-12), and interactions with target genes through promoter-enhancer l”
A three-dimensional map of the human genome at kilobase resolution reveals principles of chromatin looping (2014, methodology): “Recent efforts have suggested that this is an increasingly plausible goal (Sexton et al., 2012; Jin et al., 2013).”
Topologically-associating domains are stable units of replication-timing regulation (2014, positive): “New annotation of IMR90 TADs was performed by calculating an interaction directionality index for IMR90 Hi-C data 47 .”