Chromosome conformation capture techniques, particularly Hi-C, provide a comprehensive picture of the spatial chromosome organization at multiple architectural levels. The highest level of chromatin organization is represented by chromosome territories—areas of the nucleus preferentially occupied by individual chromosomes. At the finer scale, chromatin is spatially segregated into two compartments: active compartment A and inactive compartment B. Further higher resolution experiments demonstrate that individual chromosomes are partitioned into topologically associating domains (TADs), which are highly conserved units of chromosome organization, enabling regulation of gene expression. Finally, super-resolution versions of the Hi-C method reveal that the lowest level of chromatin architecture is represented by chromatin loops located at the corners of TADs or elsewhere.

Thus, the Hi-C technique enables detailed analysis of chromatin compartments, TADs and loops in multiple organisms and model systems, resulting in a deeper understanding of gene expression regulation mechanisms mediated by epigenetics. However, Hi-C analysis remains challenging both experimentally and computationally. Experimentally, the Hi-C protocol involves many complicated steps subject to variations and biases. Computationally, the Hi-C data analysis requires multi-step normalizations, filtralions and corrections to achieve reproducible results.