Predicting coarse-grained chromatin polymer properties from nucleosome-level contact data.

Abstract

Making coarse-grained chromatin models is essential to interpret experimental data and to simulate and predict chromatin organization/dynamics. It is common to model chromatin as a bead spring chain, with each bead representing lengths 1kb, 10kb, or 100kb of the genome. However, we do not know the physical dimensions (radius) of these beads and the properties (stretching elasticity, bending elasticity, etc.) of the chain. To bridge this gap, we simulated a large ensemble of chromatin configurations at near-nucleosome (200bp) resolution, consistent with recently published Micro-C data. We then systematically coarse-grained the configurations and predicted quantities essential for chromatin polymer representation. We predict the size (physical dimension) of chromatin beads for a range of scales from 1kb to 100s of kb and compute various polymer properties such as stretching elasticity, bending fluctuations, and intrinsic angle among polymer beads. Unlike the prevalent notion, we show that coarse-grained chromatin polymer beads should be considered as soft particles that can overlap, and we propose an overlap parameter. We show that accounting for such overlap is necessary to predict 3D distances from simulations accurately. Our results also show how chromatin polymer properties vary along the genome depending on the local chromatin state.