Data-driven polymer modeling reveals how scale-dependent active fluctuations shape chromatin organization

Abstract

The nature of the chromatin polymer and its properties are tightly coupled to its function. By analyzing recent microscopy data, we show that chromatin segments at [~] 10-100 kb scales exhibit anomalously broad bond-length fluctuations and acute local angles beyond the scope of existing polymer models. Using polymer simulations at nucleosome resolution and systematic coarse-graining, we show that chromatin at these scales requires a non-equilibrium description. We develop a data-constrained non-equilibrium model that explains these anomalous fluctuations, in which coarse-grained beads experience extensile, angular, and stochastic active forces. Our work provides an experimentally guided framework for incorporating active processes and suggests that the nature of activity is scale-dependent. The model quantitatively reproduces three-dimensional distance distributions across scales and enables inference of effective elastic and active parameters, providing a unified framework for active chromatin simulations and the study of its 3D organization.