TADS

Topologically associating domains (TADs) are contiguous regions of the genome within which chromatin interacts more frequently with itself than with regions outside the domain. They were identified using chromosome conformation capture technologies, notably Hi-C, in mammalian genomes and described as a key feature of three-dimensional genome organization. TADs typically span about 100 kilobases to one megabase, and they partition the genome into modular sectors that organize gene regulation in three dimensions.

Boundaries between TADs are enriched for binding sites of architectural proteins such as CTCF and cohesin, and many domains are anchored by chromatin loops at convergent CTCF motifs. While CTCF and cohesin are common boundary factors, not all borders require them, and TAD structures can be cell-type specific and nested within larger domains.

Functionally, TADs help insulate regulatory interactions, constraining enhancer–promoter communication within the same domain and thereby supporting proper gene expression patterns during development and differentiation. They provide a framework for understanding how regulatory elements influence nearby genes while limiting cross-talk with neighboring regions.

Genomic rearrangements that disrupt TAD boundaries, such as deletions, duplications, or inversions, can lead to enhancer hijacking or misexpression of genes, contributing to congenital disorders and cancer. TADs are inferred from population-averaged contact maps produced by Hi-C and related methods, and TAD calling is algorithm-dependent. Boundaries can vary with sequencing depth, cell type, and analysis approach, so TADs are best viewed as a flexible, hierarchical feature of 3D genome organization rather than immutable compartments.