A high-resolution map of the three-dimensional chromatin interactome in human cells was generated using Hi-C, a genome-wide chromosome conformation capture technique. The study identified over one million long-range chromatin interactions at a resolution of 5–10 kb in human fibroblasts. The results revealed general principles of chromatin organization at different genomic features and showed that TNF-α responsive enhancers are already in contact with their target promoters before signaling. This pre-existing chromatin looping is a strong predictor of gene induction and suggests that the three-dimensional chromatin landscape is stable and influences gene selection or activation by transcription factors in a cell-specific manner. The study also characterized the dynamics of promoter-enhancer contacts in response to TNF-α signaling. Hi-C experiments were performed on primary human fibroblast cells (IMR90) before and after 1 hour of TNF-α treatment, yielding ~3.4 billion uniquely mapped paired-end reads. An improved data filtering strategy was developed to identify high-confidence chromatin looping interactions, resulting in over 500 million read pairs. The analysis revealed asymmetric distribution of cis-contacts from highly expressed promoters to the immediate downstream gene bodies, which is reminiscent of interactions between exons and promoters. The study developed an algorithm to identify statistically significant looping interactions centered on a given genomic region from Hi-C contact matrices. Applying this method to the CCL2 locus, the researchers identified distal enhancers and CTCF binding sites interacting with the CCL2 promoter. The algorithm also identified previously reported long-range chromatin interactions at the HoxA gene cluster and the SHH locus, which were not readily observable from lower resolution analysis. The study characterized chromatin interactions centered on cis-elements annotated in the IMR90 cell genome. Chromatin looping interactions were significantly enriched at cis-regulatory elements, especially active promoters, enhancers, and CTCF binding sites. The results suggest that DNA looping could occur after enhancer priming by H3K4me1 but before further activation. CTCF binding sites tend to occur over a longer range than other types of cis-elements, confirming recent results from selected loci. The study identified 1,116,312 chromatin interactions with a false discovery rate of 0.1 in the human genome. The results showed that strong interactions supported by lower p-values and higher contact frequencies are more reproducible between biological replicates. The sizes of the identified interacting DNA loci range from several hundred base pairs to over 50 kb, with a median of 10.5 kb. Most chromatin interactions in IMR90 cells are located within the same topological domains. The study identified 57,585 promoter tethered regions (PTRs) in IMR90 cells, identifying 29,132 enhancer-promoter (EP) pairs involving 6,133 active promotersA high-resolution map of the three-dimensional chromatin interactome in human cells was generated using Hi-C, a genome-wide chromosome conformation capture technique. The study identified over one million long-range chromatin interactions at a resolution of 5–10 kb in human fibroblasts. The results revealed general principles of chromatin organization at different genomic features and showed that TNF-α responsive enhancers are already in contact with their target promoters before signaling. This pre-existing chromatin looping is a strong predictor of gene induction and suggests that the three-dimensional chromatin landscape is stable and influences gene selection or activation by transcription factors in a cell-specific manner. The study also characterized the dynamics of promoter-enhancer contacts in response to TNF-α signaling. Hi-C experiments were performed on primary human fibroblast cells (IMR90) before and after 1 hour of TNF-α treatment, yielding ~3.4 billion uniquely mapped paired-end reads. An improved data filtering strategy was developed to identify high-confidence chromatin looping interactions, resulting in over 500 million read pairs. The analysis revealed asymmetric distribution of cis-contacts from highly expressed promoters to the immediate downstream gene bodies, which is reminiscent of interactions between exons and promoters. The study developed an algorithm to identify statistically significant looping interactions centered on a given genomic region from Hi-C contact matrices. Applying this method to the CCL2 locus, the researchers identified distal enhancers and CTCF binding sites interacting with the CCL2 promoter. The algorithm also identified previously reported long-range chromatin interactions at the HoxA gene cluster and the SHH locus, which were not readily observable from lower resolution analysis. The study characterized chromatin interactions centered on cis-elements annotated in the IMR90 cell genome. Chromatin looping interactions were significantly enriched at cis-regulatory elements, especially active promoters, enhancers, and CTCF binding sites. The results suggest that DNA looping could occur after enhancer priming by H3K4me1 but before further activation. CTCF binding sites tend to occur over a longer range than other types of cis-elements, confirming recent results from selected loci. The study identified 1,116,312 chromatin interactions with a false discovery rate of 0.1 in the human genome. The results showed that strong interactions supported by lower p-values and higher contact frequencies are more reproducible between biological replicates. The sizes of the identified interacting DNA loci range from several hundred base pairs to over 50 kb, with a median of 10.5 kb. Most chromatin interactions in IMR90 cells are located within the same topological domains. The study identified 57,585 promoter tethered regions (PTRs) in IMR90 cells, identifying 29,132 enhancer-promoter (EP) pairs involving 6,133 active promoters