西亚试剂：A high-resolution map of the three-dimensional chromatin in

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

Fulai JinYan LiJesse R. DixonSiddarth SelvarajZhen YeAh Young LeeChia-An YenAnthony D. SchmittCelso A. EspinozaBing Ren

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.

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