Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases
Autor: | Jonathan Clark, Willian R. Ribeiro, Claudia Stellato, Szabina Balázsi, Renan O. Corrêa, Mariangela Spagnuolo, Zoltán Hajnády, Marc Veldhoen, Csaba Matolcsi, Alessandro Cuomo, Jérémy Denizot, Fabio Takeo Sato, Raphaël Mattiuz, Rachel Fellows, Caroline M. Ferreira, Tiziana Bonaldi, Joana Guedes, Patrick Varga-Weisz, Juri Kazakevych, Elena Stoyanova, Marco Aurélio Ramirez Vinolo, Hector Blackburn, Hélène Perée, Payal Jain, Anke Liebert, José Luís Fachi |
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Přispěvatelé: | Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), European Institute of Oncology [Milan] (ESMO), Division of Molecular Immunology, 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, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), European Institute of Oncology |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Acylation General Physics and Astronomy microbiote digestif Histones Intestinal Mucosa lcsh:Science ComputingMilieux_MISCELLANEOUS Regulation of gene expression Multidisciplinary biology Chemistry Histone deacetylase 2 Cell Cycle 3. Good health Chromatin Cell biology Histone Crotonates transcription Science histone digestive system Histone Deacetylases Article General Biochemistry Genetics and Molecular Biology acide gras à chaîne courte 03 medical and health sciences Histone H3 [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Animals Humans Nucleosome colon [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology General Chemistry Fatty Acids Volatile HCT116 Cells HDAC3 HDAC1 Gastrointestinal Microbiome Histone Deacetylase Inhibitors Mice Inbred C57BL [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics 030104 developmental biology biology.protein lcsh:Q Protein Processing Post-Translational |
Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018) Nature Communications Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.1-15. ⟨10.1038/s41467-017-02651-5⟩ Nature Communications, Nature Publishing Group, 2018, 9 (1), ⟨10.1038/s41467-017-02651-5⟩ Nature Communications (9), 1-15. (2018) |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-017-02651-5 |
Popis: | 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. |
Databáze: | OpenAIRE |
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