Structure and Dynamics of Interphase Chromosomes

Abstract

During interphase chromosomes decondense, but fluorescent in situ hybridization experiments reveal the existence of distinct territories occupied by individual chromosomes inside the nuclei of most eukaryotic cells. We use computer simulations to show that the existence and stability of territories is a kinetic effect that can be explained without invoking an underlying nuclear scaffold or protein-mediated interactions between DNA sequences. In particular, we show that the experimentally observed territory shapes and spatial distances between marked chromosome sites for human, Drosophila, and budding yeast chromosomes can be reproduced by a parameter-free minimal model of decondensing chromosomes. Our results suggest that the observed interphase structure and dynamics are due to generic polymer effects: confined Brownian motion conserving the local topological state of long chain molecules and segregation of mutually unentangled chains due to topological constraints.

Chromosome dynamics, molecular crowding, and diffusion in the interphase cell nucleus: a Monte Carlo lattice simulation study

“…We show that including chain dynamics allows larger macromolecules to penetrate the network, and we analyze the effect of local chain flexibility and possible self-crossing of the chromatin chain (e.g., induced by type II topoisomerases). We verify the relaxation time scales for interphase chromosomes recently estimated by Rosa and Everaers (2008) by a continuum model and show that molecular crowding by diffusing macromolecules can lead to anomalous diffusion but to a much lesser degree than crowding by the chromatin network. We also find that the stiffness of the network probed with diffusing particles is much lower than detected earlier in microrheology experiments (Tseng et al 2004).…”

“…After 120 s, they would still be resolvable in light microscopy. As discussed earlier by Rosa and Everaers (2008), the formation of chromatin territories can be caused by topological constraints which apply during the decondensation. Comparing the relaxation of models A and B chromosomes, we infer that the high persistence of chromatin amplifies these constraints and favors self-entanglement.…”

“…We have equilibrated the conformations of model B ten times as long as the others to make the onset of the entanglement regime visible. In a similar study by Rosa and Everaers (2008), Brownian dynamics simulations were used to investigate the decondensation of 100-Mbp chromosomes. Their result for simulated chromosomes, which are comparable to our model B chains, is represented by the black dots in Fig.…”

Density effects in entangled solutions of linear and ring polymers

“…At the same time, we provide previously unreported evidence that dispersed colloid particles of linear size exceeding the nominal mesh size of the solution show the tendency to diffuse more rapidly in ring polymers solutions than in linear polymers ones. Intriguingly, it was recently pointed out [18,29] that the experimentally observed chromosome organization in eukaryotes should resemble a solution of ring polymers. In this respect then, enzymes and other functional macromolecular complexes which need to run and bind to specific target sequences along the genome might have greatly benefitted from the enhanced mobility stemming from the peculiar organization of the genome [48].…”

Confinement-Induced Glassy Dynamics in a Model for Chromosome Organization

“…Although the origin of chromosomal territories is controversial because equilibrium polymer configurations with many loops naturally produce segregated domains as well [14,15], a major non-equilibrium effect, glassy dynamics of the genome under strong confinement, should not be overlooked from a contributing factor in chromosome folding. The relaxation time of a polymer via disentanglement [16] (τ rep ∼ N 3 [12,13,17,18]) could be far longer, effectively permanent for higher organisms, than the cell cycle time (τ cell ) [12,13] for a large N . Furthermore, a substantial increase of polymer relaxation time is also expected in a strong confinement as is the case for DNA inside viral capsid [19] even when N is not too large.…”