The synergy between compartmentalization and motorization in chromatin architecture.

This article focuses on optimizing the Minimal Chromatin Model (MiChroM), a coarse-grained polymer physics framework, to better understand the competing mechanisms of chromatin compartmentalization and motor-driven lengthwise compaction in shaping chromosome architecture. By varying the training order and energy baselines of MiChroM’s two main potential terms—type-to-type interactions representing phase separation and the ideal chromosome (IC) potential representing motor activity—the study reveals that increasing motor-driven compaction reduces polymer entanglements and alters inter-chromosomal contact patterns without disrupting intra-chromosomal compartmentalization. Simulations of single and multiple human chromosomes demonstrate that balancing these energy terms is crucial for accurately reproducing experimental Hi-C contact maps, particularly improving the modeling of inter-chromosomal interactions and chromosome territory formation. The findings highlight the importance of integrating both phase separation and motorization effects in theoretical models to capture genome organization and suggest avenues for extending MiChroM to include nuclear body interactions for whole-nucleus simulations.