A simple biophysical model emulates budding yeast chromosome condensation

Abstract

Mitotic chromosomes were one of the first cell biological structures to be described, yet their molecular architecture remains poorly understood. We have devised a simple biophysical model of a 300 kb-long nucleosome chain, the size of a budding yeast chromosome, constrained by interactions between binding sites of the chromosomal condensin complex, a key component of interphase and mitotic chromosomes. Comparisons of computational and experimental (4C) interaction maps, and other biophysical features, allow us to predict a mode of condensin action. Stochastic condensin-mediated pairwise interactions along the nucleosome chain generate native-like chromosome features and recapitulate chromosome compaction and individualization during mitotic condensation. Higher order interactions between condensin binding sites explain the data less well. Our results suggest that basic assumptions about chromatin behavior go a long way to explain chromosome architecture and are able to generate a molecular model of what the inside of a chromosome is likely to look like.DOI: http://dx.doi.org/10.7554/eLife.05565.001

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

“…Two, non-mutually exclusive models have been proposed: cohesin stochastically tethers different DNA segments on the same chromosome (stochastic pairwise interactions) or the ring generates a chromatin loop by extruding a chromatin fiber via a passive or active mechanism (loop extrusions) [76,77]. Cohesin often establishes chromatin loops between enhancers and promoters [8].…”

Optimisation of a Molecular Dynamics Simulation of Chromosome Condensation

“…It is easy to see that when two particles are separated by a distance greater than r c along any single axis (or any unit vector⃗ v), the Euclidean distance between them cannot possibly be less than r c . This is formalised for two particle position vectors ⃗ a and ⃗ b and an arbitrary⃗ v in Equation 1. It follows that if one were to order the particles by their scalar projection onto such a vector, then for each particle there would exist a contiguous block of particles extending either side within r c along⃗ v. Only particles within this block could possibly be within r c in space (subject to a full distance check).…”

“…This reduces the number of distance checks that must be performed to only a small neighbourhood of partitions. This was the approach used by Cheng et al [1].…”

“…The initial dataset described by Cheng et al [1] was derived from a budding yeast cell and contains 2000 nucleosomes. As no larger real datasets were available while this work was being undertaken, we generated extended versions of the original using probabilistic methods.…”

“…In this paper we discuss optimisations applied to one such biophysical molecular dynamics simulation, developed recently by Cheng et al [1]. The simulation is used to study the effects of different models of condensin interaction on the condensation of conformations of nucleosomes and linker DNA determined via in vitro methods (see Figure 1).…”