Histone H3 as a redox switch in the nucleosome core particle: insights from molecular modeling

Histones post-translational modifications are major regulators of the chromatin dynamics. Understanding the structural signature of these marks in the nucleosome context is of major importance to unravel their mechanisms of action and open perspectives for the development of new therapies. In this work, we rely on multi-microseconds molecular dynamics simulations and advanced structural analysis to unravel the effect of two modifications of the histone H3: S-sulfenylation and S-nitrosylation. These oxidative modifications are known to target the cysteine 110 on the histone H3, but there their effect on the nucleosome dynamics. In this study, we show that in a nucleosome core particle, S-sulfenylation and S-nitrosylation exhibit different structural signatures, which suggests that they play a different function. While S-sulfenylation destabilizes DNA-histone communication at the dyad and could be linked to the promotion of nucleosome disassembly events, S-nitrosylation exhibits a mild effect on the nucleosome dynamics and might have a different function. Our results highlight the fine tune link between the chemical nature of histone core post-translational modifications and their impact on the nucleosomes large architecture. We provide new insights into the regulatory mechanisms of histone oxidative modifications, about which very little is known so far.