A considerable share of hyper-acetylated peaks was located in super-enhancer regions (~21-25%) (Fig. 3B-D), and ~20% of super-enhancers contained a hyper-acetylated region after 24 hours of butyrate treatment (Supplementary Fig. 5C). Yet, only ~0.4% of hyper-acetylated super-enhancers were linked to transcriptionally upregulated genes, similar to hyper-acetylated typical enhancers and TSS regions (Supplementary Fig. 5D). Instead, weak hyper-acetylation (i.e. not passing our thresholds for differential enrichment) at typical enhancers may better explain why expression is induced at such genes (Supplementary Fig. 5E, F).
In summary, these data indicate that super-enhancers are an important target of butyrate-induced HDAC inhibition, most often resulting in a loss of H3K27Ac and correlating with reduced expression of many associated key mast cell genes.