A Compendium of Chromatin Contact Maps Reveal Spatially Active Regions in the Human Genome

The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, however, genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we discover genomic regions that exhibit unusually high levels of local chromatin interactions. These frequently interacting regions (FIREs) are enriched for active enhancers and are located near tissue-specifically expressed genes. Unlike previously identified chromatin loops, FIREs tend to engage in promiscuous local chromatin interactions in a tissue-specific manner. FIRE formation is dependent on the Cohesin complex. Additionally, we show that FIREs can help annotate function of non-coding sequence variants. The study contains new Hi-C datasets in 11 primary adult tissues. 4 of the 11 tissues have biological replicates, which is defined as two datasets from the same tissue type but from different donor individuals.The study also contains analysis of 3 previously published tissue Hi-C datasets (Leung et al., 2015), as well as several other cell lines from other studies as noted throughout our study. The study also contains the re-analysis and integration of previously published RNA-seq by the Roadmap Epigenomics Consortium (GEO database under accession number GSE16256 and from SRA database under accession umber SRP000941). all the Hi-C data generated in this study can be visualized in 3dgenome.org