show Abstracthide AbstractWe use in situ Hi-C to probe the three-dimensional architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1-kilobase resolution. We find that genomes are partitioned into local domains, which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ~10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs ‘facing’ one another. The inactive X-chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. Overall design: in situ Hi-C and dilution Hi-C were used to probe the three-dimensional structure of the genome in eight diverse human cell types and one mouse cell type. Detailed information about all files (and file formats) uploaded to GEO for this study can be found in the supplementary file 'GSE63525_OVERALL_README.rtf'.