The paper introduces Hi-C, a method for comprehensively detecting chromatin interactions in the mammalian nucleus. Based on Chromosome Conformation Capture, Hi-C crosslinks chromatin with formaldehyde, digests and ligates DNA fragments, and enriches chimeric DNA ligation junctions using biotin labeling. This method, compatible with next-generation sequencing platforms, allows for the detection of chromatin interactions on a large scale, providing spatial context to genomic studies. The authors detail the Hi-C protocol, including cell culture, crosslinking, ligation, purification, quality control, and sequencing. They also discuss expected results, data visualization, and comparisons with other methods. Hi-C offers a powerful tool for studying nuclear organization, chromosome architecture, and the biophysics of chromatin dynamics, contributing to the understanding of gene regulation and disease.The paper introduces Hi-C, a method for comprehensively detecting chromatin interactions in the mammalian nucleus. Based on Chromosome Conformation Capture, Hi-C crosslinks chromatin with formaldehyde, digests and ligates DNA fragments, and enriches chimeric DNA ligation junctions using biotin labeling. This method, compatible with next-generation sequencing platforms, allows for the detection of chromatin interactions on a large scale, providing spatial context to genomic studies. The authors detail the Hi-C protocol, including cell culture, crosslinking, ligation, purification, quality control, and sequencing. They also discuss expected results, data visualization, and comparisons with other methods. Hi-C offers a powerful tool for studying nuclear organization, chromosome architecture, and the biophysics of chromatin dynamics, contributing to the understanding of gene regulation and disease.