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).