Anomalous diffusion, spatial coherence, and viscoelasticity from the energy landscape of human chromosomes
Michele Di Pierro, Davit A. Potoyan, Peter G. Wolynes, and José N. Onuchic
PNAS July 9, 2018. 201806297; published ahead of print July 9, 2018. https://doi.org/10.1073/pnas.1806297115
Contributed by José N. Onuchic, June 8, 2018 (sent for review April 12, 2018; reviewed by Olga K. Dudko and Andrew J. Spakowitz)
Significance
Several active processes operate on eukaryotic genomes, dictating their three-dimensional arrangement and dynamical properties. The combination of structural organization and dynamics is essential to the proper functioning of the cell. We show that an effective energy landscape model for chromatin provides a unifying description of both the structural and dynamical aspects of the genome, recapitulating many of its features. Using this quasi-equilibrium energy landscape model, we demonstrate that the physical interactions accounting for genome architecture also lead to the nontrivial dynamical behavior of genomes previously described in multiple experimental observations.
Abstract
The nucleus of a eukaryotic cell is a nonequilibrium system where chromatin is subjected to active processes that continuously rearrange it over the cell’s life cycle. Tracking the motion of chromosomal loci provides information about the organization of the genome and the physical processes shaping that organization. Optical experiments report that loci move with subdiffusive dynamics and that there is spatially coherent motion of the chromatin. We recently showed that it is possible to predict the 3D architecture of genomes through a physical model for chromosomes that accounts for the biochemical interactions mediated by proteins and regulated by epigenetic markers through a transferable energy landscape. Here, we study the temporal dynamics generated by this quasi-equilibrium energy landscape assuming Langevin dynamics at an effective temperature. Using molecular dynamics simulations of two interacting human chromosomes, we show that the very same interactions that account for genome architecture naturally reproduce the spatial coherence, viscoelasticity, and the subdiffusive behavior of the motion in interphase chromosomes as observed in numerous experiments. The agreement between theory and experiments suggests that even if active processes are involved, an effective quasi-equilibrium landscape model can largely mimic their dynamical effects.
chromatin dynamics anomalous diffusion genome architecture phase separation dynamically associated domains
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