Techniques to detect physical interactions between genomic regions

Chromatin forms specific intranuclear structures through physical interactions between specific genomic regions mediated by DNA-binding proteins and/or RNAs. Recent efforts have revealed that these genome organizations and dynamics are involved in various functions of genomic DNA, such as regulation of gene expression, DNA replication, cell division, and epigenetic memory, which are mechanisms underlying cell differentiation and disease development. The methods to detect physically interacting chromatin regions and reconstruct 3D genomic organization can be roughly categorized into four types: (i) microscopic observation of visualized intranuclear structures, (ii and iii) sequencing-based methods including proximity ligation-dependent/independent methods, and (iv) de novo prediction from genomic sequences and other omics data. Here, we review these techniques to detect physical interactions between genomic regions, highlighting their unique advantages and limitations.