H3K115 marks fragile nucleosomes at regulatory sites [ATAC-seq]

Acetylation of lysine residues in the tail domain of histone H3 at active regulatory elements are well characterised, but the less studied acetylations of histone globular domain lysines also hold regulatory potential based on their potential impact on nucleosome dynamics and stability. Here we have mapped the genome-wide distribution of acetylated H3 lysine 115 (H3K115ac), a residue on the lateral surface of the nucleosomes, in mouse embryonic stem cells. We find that H3K115ac is associated with highly active promoters, especially those associated with CpG islands, and with enhancers. H3K115ac is dynamic, changing in line with gene activation during differentiation and correlated with changes in local chromatin accessibilityas assyed by ATAC-seq. Distinct from other commony studied histone acetylation marks, H3K115ac is enriched on non-canonical “fragile” nucleosomes precisely at the transcription start sites of active gene promoters and within the binding sites of pluripotency transcription factors. Surprisingly we also detect H3K115ac-marked fragile nucleosomes at sites most strongly occupied by CTCF, within the CTCF footprint and oriented relative to the CTCF motif. This unique enrichment and genomic distribution of modified fragile nucleosomes suggests a previously unappreciated role for H3K115ac in gene regulation and chromatin structure. We propose that H3K115ac is a very precise marker for identifying regulatory elements in mammalian genomes.