These data reveal that butyrate – despite its potent capacity for HDAC inhibition – affects histone acetylation at a relatively small subset (i.e. ~30%) of pre-existing H3K27Ac+ chromatin regions. Strikingly, butyrate-induced HDAC inhibition preferentially reduces H3K27Ac levels at TSSs, while H3K27Ac enrichment primarily occurs at locations distal from TSS regions, co-localizing with typical enhancers and super-enhancers.