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

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

Cold spells in the Nordic Seas during the early Eocene Greenhouse

Abstract The early Eocene (c. 56 - 48 million years ago) experienced some of the highest global temperatures in Earth’s history since the Mesozoic, with no polar ice. Reports of contradictory ice-rafted erratics and cold water glendonites in the higher latitudes have been largely dismissed due to ambiguity of the significance of these purported cold-climate indicators. Here we apply clumped isotope paleothermometry to a traditionally qualitative abiotic proxy, glendonite calcite, to generate quantitative temperature estimates for northern mid-latitude bottom waters. Our data show that the glendonites of the Danish Basin formed in waters below 5 °C, at water depths of &lt;300 m. Such near-freezing temperatures have not previously been reconstructed from proxy data for anywhere on the early Eocene Earth, and these data therefore suggest that regionalised cool episodes punctuated the background warmth of the early Eocene, likely linked to eruptive phases of the North Atlantic Igneous Province.</jats:p