Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02651-5
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Funding
- UK Biotechnology and Biological Sciences Research Council (BBSRC)
- UK Medical Research Council [MR/N009398/1]
- Brazil-BBSRC Pump-priming award [BB/N013565/1]
- Science Policy Committee
- Babraham Institute
- NC3R [NC/L001217/1]
- FAPESP [2012/10653-9, 2015/50379-1, 2015/14105-4]
- Italian Association for Cancer Research (AIRC)
- Italian Ministry of Health [RF-GR2011]
- EPIGEN flagship project grant
- Erasmus+ programme
- BBSRC
- Biotechnology and Biological Sciences Research Council [BB/N013565/1, BBS/E/B/000C0427, BB/E021638/1, BBS/E/B/000C0409, BBS/E/B/0000C338, BB/L026988/1, BBS/E/B/000C0404] Funding Source: researchfish
- Medical Research Council [G0801156, G0701175, 1858184, MR/N009398/1, 1642099] Funding Source: researchfish
- BBSRC [BBS/E/B/000C0404, BB/L026988/1, BBS/E/B/0000C338, BB/N013565/1, BBS/E/B/000C0427, BB/E021638/1, BBS/E/B/000C0409] Funding Source: UKRI
- MRC [G0801156, G0701175, MR/N009398/1] Funding Source: UKRI
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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.
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