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

• Published in: Nature communications Vol. 9; no. 1; p. 105
• Main Authors: Fellows, Rachel, Denizot, Jérémy, Stellato, Claudia, Cuomo, Alessandro, Jain, Payal, Stoyanova, Elena, Balázsi, Szabina, Hajnády, Zoltán, Liebert, Anke, Kazakevych, Juri, Blackburn, Hector, Corrêa, Renan Oliveira, Fachi, José Luís, Sato, Fabio Takeo, Ribeiro, Willian R., Ferreira, Caroline Marcantonio, Perée, Hélène, Spagnuolo, Mariangela, Mattiuz, Raphaël, Matolcsi, Csaba, Guedes, Joana, Clark, Jonathan, Veldhoen, Marc, Bonaldi, Tiziana, Vinolo, Marco Aurélio Ramirez, Varga-Weisz, Patrick
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group UK 09-01-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/109; 13/51; 38; 38/23; 42; 631/208/199; 631/337/100/1701; 631/337/100/2285; 631/443/319/320; 64; 64/60; 82/29; Acylation; Animal genetics; Animals; Biochemistry, Molecular Biology; Cell Cycle; Chains; Chromatin; Colon; Colon - metabolism; Colon - microbiology; Crotonates - metabolism; Digestive system; Fatty acids; Fatty Acids, Volatile - physiology; Gastrointestinal Microbiome; Gastrointestinal tract; Gene expression; Gene regulation; Genetics; Genetics & genetic processes; Genomics; Génétique & processus génétiques; HCT116 Cells; HDAC2 protein; Histone deacetylase; Histone Deacetylase Inhibitors; Histone Deacetylases - metabolism; Histone H3; Histones - metabolism; Humanities and Social Sciences; Humans; Intestinal microflora; Intestinal Mucosa - metabolism; Life Sciences; Lysine; Male; Metabolism; Mice, Inbred C57BL; Microbiota; Molecular biology; multidisciplinary; Post-translation; Protein Processing, Post-Translational; Science; Science (multidisciplinary); Sciences du vivant; Small intestine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-02651-5

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.
Histone post-translational modifications are known key regulators of gene expression. Here, the authors characterize histone crotonylation at histone H3 lysine 18 in intestinal epithelia and find that it is a highly dynamic cell cycle regulated mark under the regulation of the HDAC deacetylases.