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
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