Cysteine hyperoxidation rewires communication pathways in the nucleosome and destabilizes the dyad

Abstract

Gene activity is tightly controlled by reversible chemical modifications called epigenetic marks, which are of various types and modulate gene accessibility without affecting the DNA sequence. Despite an increasing body of evidence demonstrating the role of oxidative-type modifications of histones in gene expression regulation, there remains a complete absence of structural data at the atomistic level to understand the molecular mechanisms behind their regulatory action. Owing to s time-scale MD simulations and protein communication networks analysis, we describe the impact of histone H3 hyperoxidation (i.e., S-sulfonylation) on the nucleosome dynamics. Our results reveal the atomic-scale details of the intrinsic structural networks within the canonical histone core and their perturbation by hyperoxidation of the histone H3 C110. We show that this modification involves local rearrangement of the communication networks and destabilizes the dyad, which could be important for nucleosome disassembly.