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• W2065006553 abstract "A novel approach to analyse high-depth Hi-C data provides a comprehensive chromatin interaction map at approximately 5–10 kb resolution in human fibroblasts; this reveals that TNF-α-responsive enhancers are already in contact with target promoters before signalling and that this chromatin looping is a strong predictor of gene induction. Hi-C is a genomic technology based on chromosome conformation capture (3C) that can identify long-range looping interactions of chromatin throughout the genome in an unbiased fashion. Bing Ren and colleagues have developed a novel analysis pipeline for Hi-C data sets that offers much improved resolution so that interactions between cis-regulatory elements such as enhancers and promoters can be defined. Applying it to study dynamic chromatin interactions during NF-κB signalling in human fibroblasts, they find that the majority of interactions between enhancers and promoters have already formed prior to the binding of sequence-specific transcription factors to enhancers. The regulatory targets of the transcription factor thus appear to have been hardwired into the chromatin architecture. A large number of cis-regulatory sequences have been annotated in the human genome1,2, but defining their target genes remains a challenge3. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques4. 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)5. 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." @default.
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• W2065006553 date "2013-10-20" @default.
• W2065006553 modified "2023-10-10" @default.
• W2065006553 title "A high-resolution map of the three-dimensional chromatin interactome in human cells" @default.
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• W2065006553 doi "https://doi.org/10.1038/nature12644" @default.
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