Mapping physical interactions between distal parts of the genome is vital for better understanding the three-dimensional organization of the genome and its effects on cell and tissue-specific gene regulation. In phase III of ENCODE, cohesin-bound chromatin loops were mapped in 24 cell types1 using the chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) assay, to compare the frequency of these loops between cell types and, by integrating these data with H3K27ac chromatin immunoprecipitation with sequencing (ChIP–seq) and RNA sequencing (RNA-seq) data, to study the interdependency of chromatin looping, regulatory elements and gene expression. By pooling the ChIA-PET data sets from all 24 cell types, the authors detected 124,830 loops in total, which fell into two broad categories: non-variable and those that varied between cell types (about 28%). Principal component analysis of the interaction frequencies grouped the cell types into three main clusters: blood, stem-cell like (embryonic) and solid-tissue-derived. Motifs for transcription factors (TFs) that are important for cell fate determination were enriched at cell-type-specific loops — for example, SPI1/PU.1 in lymphoid cells. Furthermore, assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicated that open chromatin was enriched at these TF motifs in a cell-type-specific manner. Loop ends with many interactions in the pan-cell-type data showed overlap with enhancers (marked by H3K27ac), and loop interaction frequencies were modestly associated with the level of gene expression. When single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) for 86 traits were intersected with group-specific loop ends, blood-specific loops were found to be enriched for SNPs associated with autoimmune disease, which in turn were depleted at embryonic-specific loops. This atlas of loop data for 24 cell types, generated and analysed to the same reproducible standard, provides insights into cell-specific differences in chromatin looping, its impact on gene regulation, and the linkage of GWAS loci to relevant cell types.