Acetylation of H3K115 at the nucleosome dyad is associated with fragile nucleosomes at active regulatory sites

Acetylation of lysine residues in the tail domain of histone H3 is well characterized. However, acetyl-lysines in the histone globular domain also hold regulatory potential because of their impact on nucleosome dynamics and stability. In this study, we report the genome-wide distribution of acetylated H3 lysine 115 (H3K115ac), a residue on the lateral surface at the nucleosome dyad, in mouse embryonic stem cells. We find that H3K115ac is associated with highly active promoters, particularly those associated with CpG islands, and with enhancers. During differentiation H3K115ac is dynamic, changing in line with gene activation and chromatin accessibility. Most strikingly, unlike other commonly studied histone acetylation marks, H3K115ac is enriched on “fragile” nucleosomes within the nucleosome depleted regions of active promoters, and enhancers where it coincides with transcription factor binding. Additionally, we detect H3K115ac-marked fragile nucleosomes at sites most strongly occupied by CTCF, within the CTCF footprint and oriented relative to the CTCF motif. This unusual genomic distribution suggests that H3K115ac could have a role in nucleosome destabilization and that it might be a valuable marker for identifying functionally important regulatory elements in mammalian genomes.