Topological constraints strongly affect chromatin reconstitution in silico

C. A. Brackley, James Allan, David Keszenman Pereyra, D. Marenduzzo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The fundamental building block of chromatin, and of chromosomes, is the nucleosome, a composite material made up from DNA wrapped around a histone octamer. In this study we provide the first computer simulations of chromatin self-assembly, starting from DNA and histone proteins, and use these to understand the constraints which are imposed by the topology of DNA molecules on the creation of a polynucleosome chain. We take inspiration from the in vitro chromatin reconstitution protocols which are used in many experimental studies. Our simulations indicate that during self-assembly, nucleosomes can fall into a number of topological traps (or local folding defects), and this may eventually lead to the formation of disordered structures, characterised by nucleosome clustering. Remarkably though, by introducing the action of topological enzymes such as type I and II topoisomerase, most of these defects can be avoided and the result is an ordered 10-nm chromatin fibre. These findings provide new insight into the biophysics of chromatin formation, both in the context of reconstitution in vitro and in terms of the topological constraints which must be overcome during de novo nucleosome formation in vivo, e.g. following DNA replication or repair.

Original languageEnglish
Pages (from-to)63-73
Number of pages11
JournalNucleic Acids Research
Volume43
Issue number1
DOIs
Publication statusPublished - 1 Oct 2014

Fingerprint Dive into the research topics of 'Topological constraints strongly affect chromatin reconstitution in silico'. Together they form a unique fingerprint.

Cite this