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

Fellows, R and Denizot, J and Stellato, C and Cuomo, A and Jain, P and Stoyanova, E and Balázsi, S and Hajnády, Z and Liebert, A and Kazakevych, J and Blackburn, H and Corrêa, RO and Fachi, JL and Sato, FT and Ribeiro, WR and Ferreira, CM and Perée, H and Spagnuolo, M and Mattiuz, R and Matolcsi, C and Guedes, J and Clark, J and Veldhoen, M and Bonaldi, T and Vinolo, MAR and Varga Weisz, PD (2018) 'Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.' Nature Communications, 9. ISSN 2041-1723

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Abstract

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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Depositing User: Elements
Date Deposited: 18 Sep 2018 10:11
Last Modified: 01 Aug 2019 13:20
URI: http://repository.essex.ac.uk/id/eprint/23040

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