Fermentation

Histone code

Histone H1

Gene

Histone methyltransferase

Histone deacetylase 5

Histone H3

Butyrate

Histone deacetylase

HDAC11

Biochemistry

Histone H2A

Histone

Histone deacetylase 2

Chromatin

Nucleosome

Biology

Cell biology

Nature Communications

The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases