Conte, M.; Abraham, A.; Esposito, A.; Yang, L.; Gibcus, J. H.; Parsi, K. M.; Vercellone, F.; Fontana, A.; Di Pierno, F.; Dekker, J.; Nicodemi, M.

Here, we employ polymer physics models of chromatin to investigate the 3D folding of a 2Mb wide genomic region encompassing the human LTN1 gene, a crucial DNA locus involved in key cellular functions. Through extensive Molecular Dynamics simulations, we reconstruct in-silico the ensemble of single-molecule LTN1 3D structures, which we benchmark against recent in-situ Hi-C 2.0 data. The model-derived single molecules are then used to predict structural folding features at the single-cell level, providing testable predictions for super-resolution microscopy experiments.