Butyrate triggers global histone hyperacetylation
To map the epigenomic landscape of two primary human mast cell cultures, D1 and D2, after butyrate treatment, we performed ChIP-Seq specific for histone 3 lysine 27 acetylation (H3K27Ac) and histone 3 lysine 4 dimethylation (H3K4Me2) after 0, 3, 12 and 24 h of butyrate treatment. H3K27Ac is a well-characterized acetylation mark that strongly correlates with transcriptional activity; H3K4Me2 is also associated with active genes yet is not an HDAC target34. Genome-wide H3K27Ac coverage was markedly increased by butyrate (up to ~2.6 fold), which was already apparent after 3 h and remained elevated after 24 h of treatment (Fig. 2A, left panel). The relative increase in H3K27Ac+ regions across the genome was essentially independent of enrichment calling parameter settings (Supplementary Fig. 2A), and the location of these hyperacetylated regions was largely consistent between different donors (Fig. 2A, ‘Shared’ peaks). Butyrate treatment did not affect overall coverage of H3K4Me2 (Fig. 2A, right panel, Supplementary Fig. 2B), a histone mark also associated with active chromatin yet not an HDAC target. In addition to coverage per megabase (Mb) of DNA, butyrate treatment increased the number of individually called H3K27Ac peaks in primary human mast cells ~2.6-fold (from 54,710 to 143,799) after 24 h, while H3K4Me2 peaks showed a much more modest increase (~1.3-fold, from 80,219 to 105,037 at 24 h) (Fig. 2B). Furthermore, butyrate treatment shifted the relative abundance of acetylation at genomic locations from TSS regions (from ~17% down to ~10%) to intronic and intergenic regions (Supplementary Fig. 2B).