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Nat Commun. 2018 Jan 9;9(1):105. doi: 10.1038/s41467-017-02651-5.

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

Author information

1
Nuclear Dynamics, Babraham Institute, Cambridge, CB22 3AT, UK.
2
Université Clermont Auvergne, Inserm U1071, INRA USC2018, M2iSH, Clermont-Ferrand, F-63000, France.
3
Department of Experimental Oncology, Istituto Europeo di Oncologia, 20139, Milano, Italy.
4
Laboratory of Immunoinflammation, Institute of Biology, UNICAMP, Campinas, 13083-862, Brazil.
5
Department of Pharmaceutical Sciences, Institute of Environmental, Chemistry and Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, SP, 09913-03, Brazil.
6
Chemical Biology Graduate Program, Universidade Federal de São Paulo, Diadema, SP, 09913-03, Brazil.
7
Lymphocyte Signalling and Development, Babraham Institute, Cambridge, CB22 3AT, UK.
8
Biological Chemistry, Babraham Institute, Cambridge, CB22 3AT, UK.
9
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, 1649-028, Portugal.
10
Department of Experimental Oncology, Istituto Europeo di Oncologia, 20139, Milano, Italy. tiziana.bonaldi@ieo.it.
11
Laboratory of Immunoinflammation, Institute of Biology, UNICAMP, Campinas, 13083-862, Brazil. mvinolo@unicamp.br.
12
Nuclear Dynamics, Babraham Institute, Cambridge, CB22 3AT, UK. patrick.varga-weisz@babraham.ac.uk.
13
School of Biological Sciences, University of Essex, Colchester, CO4 3SQ, UK. patrick.varga-weisz@babraham.ac.uk.

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.

PMID:
29317660
PMCID:
PMC5760624
DOI:
10.1038/s41467-017-02651-5
[Indexed for MEDLINE]
Free PMC Article

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