Nucleosome-induced homology recognition in chromatin

Author:

Hedley Jonathan G.1ORCID,Teif Vladimir B.2ORCID,Kornyshev Alexei A.1ORCID

Affiliation:

1. Department of Chemistry, Faculty of Natural Sciences, Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London W12 0BZ, UK

2. School of Life Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK

Abstract

One of the least understood properties of chromatin is the ability of its similar regions to recognize each other through weak interactions. Theories based on electrostatic interactions between helical macromolecules suggest that the ability to recognize sequence homology is an innate property of the non-ideal helical structure of DNA. However, this theory does not account for the nucleosomal packing of DNA. Can homologous DNA sequences recognize each other while wrapped up in the nucleosomes? Can structural homology arise at the level of nucleosome arrays? Here, we present a theoretical model for the recognition potential well between chromatin fibres sliding against each other. This well is different from the one predicted for bare DNA; the minima in energy do not correspond to literal juxtaposition, but are shifted by approximately half the nucleosome repeat length. The presence of this potential well suggests that nucleosome positioning may induce mutual sequence recognition between chromatin fibres and facilitate the formation of chromatin nanodomains. This has implications for nucleosome arrays enclosed between CTCF–cohesin boundaries, which may form stiffer stem-like structures instead of flexible entropically favourable loops. We also consider switches between chromatin states, e.g. through acetylation/deacetylation of histones, and discuss nucleosome-induced recognition as a precursory stage of genetic recombination.

Funder

Engineering and Physical Sciences Research Council

Wellcome Trust

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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