Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays

TL;DR

This study reanalyzed HP1 binding to nucleosomal arrays, showing that binding behavior depends on nucleosome repeat length and array structure rather than direct cooperative interactions between HP1 dimers.

Contribution

It introduces a simplified model explaining HP1 binding without cooperative interactions and highlights the influence of nucleosome array structure on binding stoichiometry.

Findings

Binding stoichiometry depends on nucleosome repeat length.

Longer DNA linkers increase available binding sites.

Nucleosome array folding affects HP1 binding sites.

Abstract

Heterochromatin protein 1 (HP1) participates in establishing and maintaining heterochromatin via its histone modification dependent chromatin interactions. In recent papers HP1 binding to nucleosomal arrays was measured in vitro and interpreted in terms of nearest-neighbor cooperative binding. This mode of chromatin interactions could lead to spreading of HP1 along the nucleosome chain. Here, we reanalyzed previous data by representing the nucleosome chain as a one-dimensional binding lattice, and show how the experimental HP1 binding isotherms can be explained by a simpler model without cooperative interactions between neighboring HP1 dimers. Based on these calculations and spatial models of dinucleosomes and nucleosome chains, we propose that binding stoichiometry is dependent of the nucleosome repeat length (NRL) rather than protein interactions between HP1 dimers. According to our calculations, more open nucleosome arrays with long DNA linkers are characterized by a larger number of binding sites in comparison to chains with short NRL. Furthermore, we demonstrate by Monte Carlo simulations that the NRL dependent folding of the nucleosome chain can induce allosteric changes of HP1 binding sites. Thus, HP1 chromatin interactions can be modulated by the change of binding stoichiometry and type of binding to condensed (methylated) and non-condensed (unmethylated) nucleosome arrays in the absence of direct interactions between HP1 dimers.