The synergy between compartmentalization and motorization in chromatin architecture.

Abstract

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.