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

Author

Listed:
  • Rachel Fellows

    (Babraham Institute)

  • Jérémy Denizot

    (Babraham Institute
    Université Clermont Auvergne)

  • Claudia Stellato

    (Babraham Institute)

  • Alessandro Cuomo

    (Istituto Europeo di Oncologia)

  • Payal Jain

    (Babraham Institute)

  • Elena Stoyanova

    (Babraham Institute)

  • Szabina Balázsi

    (Babraham Institute)

  • Zoltán Hajnády

    (Babraham Institute)

  • Anke Liebert

    (Babraham Institute)

  • Juri Kazakevych

    (Babraham Institute)

  • Hector Blackburn

    (Babraham Institute)

  • Renan Oliveira Corrêa

    (UNICAMP)

  • José Luís Fachi

    (UNICAMP)

  • Fabio Takeo Sato

    (UNICAMP)

  • Willian R. Ribeiro

    (Universidade Federal de São Paulo
    Universidade Federal de São Paulo)

  • Caroline Marcantonio Ferreira

    (Universidade Federal de São Paulo)

  • Hélène Perée

    (Babraham Institute)

  • Mariangela Spagnuolo

    (Babraham Institute)

  • Raphaël Mattiuz

    (Babraham Institute)

  • Csaba Matolcsi

    (Babraham Institute)

  • Joana Guedes

    (Babraham Institute)

  • Jonathan Clark

    (Babraham Institute)

  • Marc Veldhoen

    (Babraham Institute
    Faculdade de Medicina da Universidade de Lisboa)

  • Tiziana Bonaldi

    (Istituto Europeo di Oncologia)

  • Marco Aurélio Ramirez Vinolo

    (UNICAMP)

  • Patrick Varga-Weisz

    (Babraham Institute
    University of Essex)

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.

Suggested Citation

  • Rachel Fellows & Jérémy Denizot & Claudia Stellato & Alessandro Cuomo & Payal Jain & Elena Stoyanova & Szabina Balázsi & Zoltán Hajnády & Anke Liebert & Juri Kazakevych & Hector Blackburn & Renan Oliv, 2018. "Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02651-5
    DOI: 10.1038/s41467-017-02651-5
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    Cited by:

    1. Tomás Clive Barker-Tejeda & Elisa Zubeldia-Varela & Andrea Macías-Camero & Lola Alonso & Isabel Adoración Martín-Antoniano & María Fernanda Rey-Stolle & Leticia Mera-Berriatua & Raphaëlle Bazire & Pau, 2024. "Comparative characterization of the infant gut microbiome and their maternal lineage by a multi-omics approach," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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