Overlooked transcription factor crosslinking and steric forces can coordinate chromatin and TAD organization

Polymer simulations are increasingly effective at interpreting the often beautiful hierarchical patterns that arise in chromatin conformation capture (3C,Hi-C,Micro-C) assays. While a number of models and theories can reconstruct these patterns in silco, many use fitted coarse-grained potentials and ignore microscopic mechanisms involved in the interactions between chromatin, transcription factors (TFs), and the surrounding nucleoplasm. Here, I investigate how steric forces between TFs expand and isolate genomic regions, while individually modeled crosslinking proteins condense other regions. These simulations provide a microscopic interpretation of the potentials used in other methods, allowing us to explore the importance of physical constants, such as TF binding rates and binding strength, in creating specific yet stable chromatin domains.