Connecting Chromatin Structures to Gene Regulation Using Dynamic Polymer Simulations

• DOI: 10.7554/elife.94738
• Publication Date: 2024-05-09T13:25:14Z
• Authors: Yi Fu; Tianxiao Zhao; Finnegan Clark; Sofia Nomikou; Aristotelis Tsirigos; Timothée Lionnet

The transfer of regulatory information between distal loci on chromatin is thought to involve physical proximity, but key biophysical features these contacts remain unclear. For instance, it unknown how close and for long two need be in order productively interact. main challenge that currently impossible measure dynamics with high spatiotemporal resolution at scale. Polymer simulations provide an accessible rigorous way test models regulation, yet there a lack simple general methods extracting the values model parameters. Here we adapt Nelder-Mead simplex optimization algorithm select best polymer matching given Hi-C dataset, using MYC locus as example. model’s parameters predict compartmental rearrangement leukemia, which validate single-cell measurements. Leveraging trajectories predicted by model, find similar contact frequencies can exhibit widely different dynamics. Interestingly, frequency productive interactions exhibits non-linear relationship their when enforce specific capture radius duration. These observations are consistent recent experimental suggest dynamic ensemble configurations, rather than average matrices, required fully long-range interactions.