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

Autor(es):Mostrar menos -

Fellows, Rachel ^[1] ; Denizot, Jeremy ^{[1, 2]} ; Stellato, Claudia ^[1] ; Cuomo, Alessandro ^[3] ; Jain, Payal ^[1] ; Stoyanova, Elena ^[1] ; Balazsi, Szabina ^[1] ; Hajnady, Zoltan ^[1] ; Liebert, Anke ^[1] ; Kazakevych, Juri ^[1] ; Blackburn, Hector ^[1] ; Correa, Renan Oliveira ^[4] ; Fachi, Jose Luis ^[4] ; Sato, Fabio Takeo ^[4] ; Ribeiro, Willian R. ^{[5, 6]} ; Ferreira, Caroline Marcantonio ^[5] ; Peree, Helene ^[1] ; Spagnuolo, Mariangela ^[1] ; Mattiuz, Raphael ^[1] ; Matolcsi, Csaba ^[1] ; Guedes, Joana ^[7] ; Clark, Jonathan ^[8] ; Veldhoen, Marc ^{[7, 9]} ; Bonaldi, Tiziana ^[3] ; Ramirez Vinolo, Marco Aurelio ^[4] ; Varga-Weisz, Patrick ^{[10, 1]}

Afiliação do(s) autor(es)

^[1] Babraham Inst, Nucl Dynam, Cambridge CB22 3AT - England

^[2] Univ Clermont Auvergne, Inserm U1071, INRA USC2018, M2iSH, F-63000 Clermont Ferrand - France

^[3] Ist Europeo Oncol, Dept Expt Oncol, I-20139 Milan - Italy

^[4] Univ Estadual Campinas, Lab Immunoinflammat, Inst Biol, BR-13083862 Campinas, SP - Brazil

^[5] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Inst Environm Chem & Pharmaceut Sci, BR-0991303 Diadema, SP - Brazil

^[6] Univ Fed Sao Paulo, Chem Biol Grad Program, BR-0991303 Diadema, SP - Brazil

^[7] Babraham Inst, Lymphocyte Signalling & Dev, Cambridge CB22 3AT - England

^[8] Babraham Inst, Biol Chem, Cambridge CB22 3AT - England

^[9] Univ Lisbon, Inst Med Mol, Fac Med, P-1649028 Lisbon - Portugal

^[10] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex - England

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 9, JAN 9 2018.
• Citações Web of Science: 59

Resumo

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. (AU)

• Processo FAPESP: 12/10653-9 - Envolvimento dos ácidos graxos de cadeia curta e seu receptor (GPR43) na resposta imune a bactérias anaeróbias in vivo e in vitro
• Beneficiário: Marco Aurélio Ramirez Vinolo
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 15/50379-1 - Papel das modificações epigenéticas induzidas pelos AGCCs em células epiteliais intestinais
• Beneficiário: Marco Aurélio Ramirez Vinolo
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/14105-4 - Papel das modificações epigenéticas induzidas pelos AGCCs em células epiteliais intestinais
• Beneficiário: Renan Oliveira Corrêa
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Mestrado