A simple biophysical model emulates budding yeast chromosome condensation.

Tammy Mk Cheng,Sebastian Heeger,Aengus Stewart,Carmay Lim,Jon Wright,Paul A Bates,Frank Uhlmann,Raphaël Ag Chaleil,Nik Matthews

doi:10.7554/elife.05565

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.

Highlights

One of the most recognizable phenomena of dividing cells is the compaction of chromatin that occurs when cells enter mitosis
We applied a ‘bead-spring’ model in which the chromatin chain is represented as a series of nucleosome beads, joined by DNA linkers whose dynamic behavior is approximated as springs (Figure 1A)
We explore chromosome architecture by building a simple computational model of a budding yeast chromosome, consisting of coarse-grained representations of the two essential elements for condensation, nucleosomes, and a chromatin cross-linking protein, modeled in our simulations to follow the distribution and behavior of condensin

Summary

Introduction

One of the most recognizable phenomena of dividing cells is the compaction of chromatin that occurs when cells enter mitosis. Centimeters of DNA are compacted into micrometer-sized, rodshaped chromosomes. This allows genetic material to be packed small enough to be faithfully segregated to opposite cell halves, and compact enough to withstand the forces generated during this process. Condensin is a member of the structural maintenance of chromosomes (SMC) family of large ringshaped multisubunit protein complexes. These are thought to bind to DNA by topological embrace (Nasmyth and Haering, 2005; Cuylen et al, 2011; Murayama and Uhlmann, 2014)

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Results

Conclusion