Core Histone Hyperacetylation Impacts Cooperative Behavior and High-Affinity Binding of Histone H1 to Chromatin

Linker histones stabilize higher order chromatin structures and limit access to proteins involved in DNA-dependent processes. Core histone acetylation is thought to modulate HI binding. In the current study, we employed kinetic modeling of H1 recovery curves obtained during fluorescence recovery after photo-bleaching (FRAP) experiments to determine the impact of core histone acetylation on the different variants of H Following brief treatments with histone deacetylase inhibitor, most variants showed no change in HI dynamics. A change in mobility was detected only when longer treatments were used to induce high levels of histone acetylation. This hyperacetylation imparted marked changes in the dynamics of low-affinity HI population, while conferring variant-specific changes in the mobility of H I molecules that were strongly bound. Both the C-terminal domain (CTD) and globular domain were responsible for this differential response to TSA. Furthermore, we found that neither the CTD nor the globular domain, by themselves, undergoes a change in kinetics following hyperacetylation. This led us to conclude that hyperacetylation of core histones affects the cooperative nature of low-affinity H1 binding, with some variants undergoing a predicted decrease of almost 2 orders of magnitude.