A simple biophysical model emulates budding yeast chromosome condensation

Author:

Cheng Tammy MK1,Heeger Sebastian2,Chaleil Raphaël AG1,Matthews Nik3,Stewart Aengus4,Wright Jon5,Lim Carmay6,Bates Paul A1,Uhlmann Frank2

Affiliation:

1. Biomolecular Modelling Laboratory, Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, United Kingdom

2. Chromosome Segregation Laboratory, Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, United Kingdom

3. Advanced Sequencing Facility, Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, United Kingdom

4. Bioinformatics and Biostatistics Service, Lincoln's Inn Fields Laboratory, The Francis Crick Institute, London, United Kingdom

5. Genomics Research Center, Academia Sinica, Taipei, Taiwan

6. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

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.

Funder

Cancer Research UK

European Research Council

EMBO

Academia Sinica

Ministry of Science and Technology, Taiwan (MOST)

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference66 articles.

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