Nucleosome sliding can influence the spreading of histone modifications

TL;DR

This study uses a stochastic model to demonstrate how nucleosome sliding influences the spreading and patterning of histone modifications, affecting chromatin structure and gene regulation.

Contribution

It introduces a novel simulation model linking nucleosome dynamics with histone modification kinetics, revealing their combined role in chromatin organization.

Findings

Nucleosome sliding impacts histone modification patterns.

Density and sliding dynamics can create asymmetric modification profiles.

Model predictions align with experimental observations.

Abstract

Nucleosomes are the fundamental building blocks of chromatin that not only help in the folding of chromatin but also in carrying epigenetic information. It is known that nucleosome sliding is responsible for dynamically organizing chromatin structure and the resulting gene regulation. Since sliding can move two neighboring nucleosomes physically close or away, can it play a role in the spreading of histone modifications? We investigate this by simulating a stochastic model that couples nucleosome dynamics with the kinetics of histone modifications. We show that the sliding of nucleosomes can affect the modification pattern as well as the time it takes to modify a given region of chromatin. Exploring different nucleosome densities and modification kinetic parameters, we show that nucleosome sliding can be important for creating histone modification domains. Our model predicts that nucleosome density coupled with sliding dynamics can create an asymmetric histone modification profile around regulatory regions. We also compute the probability distribution of modified nucleosomes and relaxation kinetics of modifications. Our predictions are comparable with known experimental results.