title: A high-resolution map of the three-dimensional chromatin interactome in human cells.
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.
authors.affiliation: 1] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA [2].
authors.forename: Fulai
authors.initials: F
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Dixon
authors.forename: Siddarth
authors.initials: S
authors.lastname: Selvaraj
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ye
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Chia-An
authors.initials: CA
authors.lastname: Yen
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Schmitt
authors.forename: Celso A
authors.initials: CA
authors.lastname: Espinoza
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D021621:Imaging, Three-Dimensional; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002843:Chromatin; D014409:Tumor Necrosis Factor-alpha