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Understanding the mechanisms governing the structure and dynamics of flexible polymers like chromosomes, especially the signatures of motor-driven active processes, is of great interest in genome biology. We study chromosomes as a coarse-grained polymer model where microscopic motor activity is captured via an additive temporally persistent noise. The active steady state is characterized by two parameters: active force, controlling the persistent-noise amplitude, and correlation time, the decay time of active noise. We find that activity drives correlated motion over long distances and a regime of dynamic compaction into a globally collapsed entangled globule. Diminished topological constraints destabilize the entangled globule, and the active segments trapped in the globule move toward the periphery, resulting in an enriched active monomer density near the periphery. We also show that heterogeneous activity leads to the segregation of the highly dynamic species from the less dynamic one, suggesting a role of activity in chromosome compartmental segregation. Adding activity to experimental-data-derived structures, we find active loci may mechanically perturb and switch compartments established via epigenetics-driven passive self-association. The key distinguishing signatures of activity are enhanced apparent diffusivity, exploration of all the dynamic regimes (subdiffusion, effective diffusion, and superdiffusion) at various lag times, and a broadened distribution of observables like the dynamic exponents. Published by the American Physical Society2024
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This content will become publicly available on March 21, 2026
The synergy between compartmentalization and motorization in chromatin architecture
High-resolution techniques capable of manipulating from single molecules to millions of cells are combined with three-dimensional modeling followed by simulation to comprehend the specific aspects of chromosomes. From the theoretical perspective, the energy landscape theory from protein folding inspired the development of the minimal chromatin model (MiChroM). In this work, two biologically relevant MiChroM energy terms were minimized under different conditions, revealing a competition between loci compartmentalization and motor-driven activity mechanisms in chromatin folding. Enhancing the motor activity energy baseline increased the lengthwise compaction and reduced the polymer entanglement. Concomitantly, decreasing compartmentalization-related interactions reduced the overall polymer collapse, although compartmentalization given by the microphase separation remained almost intact. For multiple chromosome simulations, increased motorization intensified the territory formation of the different chains and reduced compartmentalization strength lowered the probability of contact formation of different loci between multiple chains, approximating to the experimental inter-contacts of the human chromosomes. These findings have direct implications for experimental data-driven chromosome modeling, specially those involving multiple chromosomes. The interplay between phase-separation and territory formation mechanisms should be properly implemented in order to recover the genome architecture and dynamics, features that might play critical roles in regulating nuclear functions.
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- PAR ID:
- 10597042
- Publisher / Repository:
- AIP Publishing
- Date Published:
- Journal Name:
- The Journal of Chemical Physics
- Volume:
- 162
- Issue:
- 11
- ISSN:
- 0021-9606
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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