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

Rachel Fellows, Jérémy Denizot, Claudia Stellato, Alessandro Cuomo, Payal Jain, Elena Stoyanova, Szabina Balázsi, Zoltán Hajnády, Anke Liebert, Juri Kazakevych, Hector Blackburn, Renan Oliveira Corrêa, José Luís Fachi, Fabio Takeo Sato, Willian R. Ribeiro, Caroline Marcantonio Ferreira, Hélène Perée, Mariangela Spagnuolo, Raphaël Mattiuz, Csaba MatolcsiJoana Guedes, Jonathan Clark, Marc Veldhoen, Tiziana Bonaldi, Marco Aurélio Ramirez Vinolo, Patrick Varga-Weisz

Research output: Contribution to journalArticlepeer-review


The recently discovered histone post-translational modification crotonylation connects cellularmetabolism to gene regulation. Its regulation and tissue-specific functions are poorlyunderstood. We characterize histone crotonylation in intestinal epithelia and find that histoneH3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestinecrypt and colon, and is linked to gene regulation. We show that this modification is highlydynamic 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 knownHDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation.Consistent with this, we find that depletion of the gut microbiota leads to a globalchange in histone crotonylation in the colon. Our results suggest that histone crotonylationconnects chromatin to the gut microbiota, at least in part, via short-chain fatty acids andHDACs.

Original languageEnglish
Article number105
JournalNature Communications
Issue number1
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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