Detecting higher-order chromosome interactions by polymer modeling

M Conte and S Bianco and A Esposito and A Abraham and S Guha and F Vercellone and A Fontana and F Di Pierno, EUROPEAN PHYSICAL JOURNAL PLUS, 140, 79 (2025).

DOI: 10.1140/epjp/s13360-025-06026-4

Recent experiments have revealed that human chromosomes have an intricate three-dimensional architecture in the cell nucleus, encompassing a hierarchy of interactions across multiple genomic scales. Despite those advances, detecting multiway DNA contacts at the single- molecule level remains challenging. Here, we use polymer physics models to investigate higher-order chromosomal contacts within a key genomic region in human colorectal cancer cells. By running extensive Molecular Dynamics simulations, we test model predictions against available experimental data and show that the model ensemble of single-molecule conformations significantly captures complex multiway chromosomal interactions beyond mere pairwise contacts.

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