Nucleosome Assembly State Governs Histone H3 Tail Conformation and Dynamics

Abstract

Accessibility of the human genome must be dynamically modulated for proper gene control. As such, the structure of chromatin undergoes continual temporal and spatial rearrangements during which nucleosomes, the basic structural unit of chromatin, are reorganized and DNA is repositioned around the nucleosome core. The canonical nucleosome consists of two copies each of the histones H2A, H2B, H3 and H4. Recent evidence suggests that subnucleosomal species lacking the standard number of histones exist in cells, at least as transcriptional and remodeling intermediates. Altering the composition of nucleosomes may serve as a mechanism of chromatin regulation. We recently found that the H3 tails exist in a dynamic ensemble of states within the nucleosome core particle, collapsed onto the core DNA. This results in inhibition of binding by a model histone reader domain in the absence of other nuclear factors. We sought to investigate the effects of removing one or both H2A/H2B dimers on the conformational ensemble of the H3 tails. In this study, we demonstrate that the conformation of the H3 tails is sensitive to the assembly state of the nucleosome core particle (NCP). Solution NMR studies demonstrate that the H3 tails experience distinct environments between octasomes (canonical nucleosomes), hexasomes (lacking one dimer), and tetrasomes (lacking both dimers). These studies additionally demonstrate that the accessibility of the H3 tails is influenced by the assembly state of the NCP. Altogether, these studies suggest that nucleosome assembly state is another mechanism of modulating histone tail conformation and accessibility, with implications in chromatin signaling and remodeling.