Abstract
This review explores how DNA folds into 3D higher-order chromatin structures that regulate gene activity. It highlights how epigenetic mechanisms and architectural proteins work together to shape the dynamic chromatin folding while allowing structural flexibility based on cellular needs. Disruption of these folding patterns leads to aberrant gene regulation, contributing to cancer, aging-related disorders, and certain congenital conditions. We emphasize specific genomic regions and epigenetic modulators that act as regulatory hubs for 3D organization, which could serve as promising biomarkers or therapeutic targets for cancer. Overall, it underscores the importance of a deeper understanding of DNA’s large-scale 3D architecture for advancing precision medicine and developing novel diagnostic approaches for cancer and other human diseases.