Bridging scales in chromatin organization: Computational models of loop formation and their implications for genome function.

Chromatin loop formation plays a crucial role in 3D genome interactions, with misfolding potentially leading to irregular gene expression and various diseases. While experimental tools such as Hi-C have advanced our understanding of genome interactions, the biophysical principles underlying chromatin loop formation remain elusive. This review examines computational approaches to chromatin folding, focusing on polymer models that elucidate chromatin loop mechanics. We discuss three key models: (1) the multi-loop-subcompartment model, which investigates the structural effects of loops on chromatin conformation; (2) the strings and binders switch model, capturing thermodynamic chromatin aggregation; and (3) the loop extrusion model, revealing the role of structural maintenance of chromosome complexes. In addition, we explore advanced models that address chromatin clustering heterogeneity in biological processes and disease progression. The review concludes with an outlook on open questions and current trends in chromatin loop formation and genome interactions, emphasizing the physical and computational challenges in the field.