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

Adwaith, P.; Kadam, S.; Pankar, S.; Notani, D.; Padinhateeri, R.

2026-04-29 biophysics
10.64898/2026.04.27.721044 bioRxiv
Show 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.

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