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

A large number of cis-regulatory sequences have been annotated in the human genome(1,2), but defining their target genes remains a challenge(3). One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C) based techniques(4). 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 5–10kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts upon TNF-α signaling in these cells. Unexpectedly, we found that TNF-α responsive enhancers are already in contact with their target promoters prior to signaling. Such pre-existing chromatin looping, which also exists in other cell types with different extra-cellular signaling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is rather stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.