Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/54268 http://dx.doi.org/10.1038/s41467-017-02651-5 |
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. |
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Fellows, RachelDenizot, JeremyStellato, ClaudiaCuomo, AlessandroJain, PayalStoyanova, ElenaBalazsi, SzabinaHajnady, ZoltanLiebert, AnkeKazakevych, JuriBlackburn, HectorCorrea, Renan OliveiraFachi, Jose LuisSato, Fabio TakeoRibeiro, Willian R. [UNIFESP]Ferreira, Caroline Marcantonio [UNIFESP]Peree, HeleneSpagnuolo, MariangelaMattiuz, RaphaelMatolcsi, CsabaGuedes, JoanaClark, JonathanVeldhoen, MarcBonaldi, TizianaRamirez Vinolo, Marco AurelioVarga-Weisz, Patrick2020-07-08T13:09:52Z2020-07-08T13:09:52Z2018Nature Communications. London, v. 9, p. -, 2018.2041-1723https://repositorio.unifesp.br/handle/11600/54268http://dx.doi.org/10.1038/s41467-017-02651-5WOS000419658100005.pdf10.1038/s41467-017-02651-5WOS:000419658100005The 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.UK Biotechnology and Biological Sciences Research Council (BBSRC)UK Medical Research CouncilBrazil-BBSRC Pump-priming awardScience Policy CommitteeBabraham InstituteNC3RFAPESPItalian Association for Cancer Research (AIRC)Italian Ministry of HealthEPIGEN flagship project grantErasmus+ programmeBBSRCBabraham Inst, Nucl Dynam, Cambridge CB22 3AT, EnglandIst Europeo Oncol, Dept Expt Oncol, I-20139 Milan, ItalyUniv Estadual Campinas, Lab Immunoinflammat, Inst Biol, BR-13083862 Campinas, SP, BrazilUniv Fed Sao Paulo, Dept Pharmaceut Sci, Inst Environm Chem & Pharmaceut Sci, BR-0991303 Diadema, SP, BrazilUniv Fed Sao Paulo, Chem Biol Grad Program, BR-0991303 Diadema, SP, BrazilBabraham Inst, Lymphocyte Signalling & Dev, Cambridge CB22 3AT, EnglandBabraham Inst, Biol Chem, Cambridge CB22 3AT, EnglandUniv Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, EnglandUniv Clermont Auvergne, Inserm U1071, INRA USC2018, M2iSH, F-63000 Clermont Ferrand, FranceUniv Lisbon, Inst Med Mol, Fac Med, P-1649028 Lisbon, PortugalUniv Fed Sao Paulo, Dept Pharmaceut Sci, Inst Environm Chem & Pharmaceut Sci, BR-0991303 Diadema, SP, BrazilUniv Fed Sao Paulo, Chem Biol Grad Program, BR-0991303 Diadema, SP, BrazilUK Medical Research Council: MR/N009398/1Brazil-BBSRC Pump-priming award: BB/N013565/1NC3R: NC/L001217/1FAPESP: 2012/10653-9, 2015/50379-1, 2015/14105-4Italian Ministry of Health: RF-GR2011Web of Science-engNature Publishing GroupNature CommunicationsMicrobiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLondon9info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000419658100005.pdfapplication/pdf3154795${dspace.ui.url}/bitstream/11600/54268/1/WOS000419658100005.pdf8596106ce9d518ad29fc6af3bb111e86MD51open accessTEXTWOS000419658100005.pdf.txtWOS000419658100005.pdf.txtExtracted texttext/plain84128${dspace.ui.url}/bitstream/11600/54268/8/WOS000419658100005.pdf.txtc9531953033ac15720fd54ca10e8a038MD58open accessTHUMBNAILWOS000419658100005.pdf.jpgWOS000419658100005.pdf.jpgIM Thumbnailimage/jpeg6567${dspace.ui.url}/bitstream/11600/54268/10/WOS000419658100005.pdf.jpgd993abc21a51939aaaf23c2fb2e93395MD510open access11600/542682023-06-05 19:28:51.304open accessoai:repositorio.unifesp.br:11600/54268Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:28:51Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
title |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
spellingShingle |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases Fellows, Rachel |
title_short |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
title_full |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
title_fullStr |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
title_full_unstemmed |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
title_sort |
Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases |
author |
Fellows, Rachel |
author_facet |
Fellows, Rachel Denizot, Jeremy Stellato, Claudia Cuomo, Alessandro Jain, Payal Stoyanova, Elena Balazsi, Szabina Hajnady, Zoltan Liebert, Anke Kazakevych, Juri Blackburn, Hector Correa, Renan Oliveira Fachi, Jose Luis Sato, Fabio Takeo Ribeiro, Willian R. [UNIFESP] Ferreira, Caroline Marcantonio [UNIFESP] Peree, Helene Spagnuolo, Mariangela Mattiuz, Raphael Matolcsi, Csaba Guedes, Joana Clark, Jonathan Veldhoen, Marc Bonaldi, Tiziana Ramirez Vinolo, Marco Aurelio Varga-Weisz, Patrick |
author_role |
author |
author2 |
Denizot, Jeremy Stellato, Claudia Cuomo, Alessandro Jain, Payal Stoyanova, Elena Balazsi, Szabina Hajnady, Zoltan Liebert, Anke Kazakevych, Juri Blackburn, Hector Correa, Renan Oliveira Fachi, Jose Luis Sato, Fabio Takeo Ribeiro, Willian R. [UNIFESP] Ferreira, Caroline Marcantonio [UNIFESP] Peree, Helene Spagnuolo, Mariangela Mattiuz, Raphael Matolcsi, Csaba Guedes, Joana Clark, Jonathan Veldhoen, Marc Bonaldi, Tiziana Ramirez Vinolo, Marco Aurelio Varga-Weisz, Patrick |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Fellows, Rachel Denizot, Jeremy Stellato, Claudia Cuomo, Alessandro Jain, Payal Stoyanova, Elena Balazsi, Szabina Hajnady, Zoltan Liebert, Anke Kazakevych, Juri Blackburn, Hector Correa, Renan Oliveira Fachi, Jose Luis Sato, Fabio Takeo Ribeiro, Willian R. [UNIFESP] Ferreira, Caroline Marcantonio [UNIFESP] Peree, Helene Spagnuolo, Mariangela Mattiuz, Raphael Matolcsi, Csaba Guedes, Joana Clark, Jonathan Veldhoen, Marc Bonaldi, Tiziana Ramirez Vinolo, Marco Aurelio Varga-Weisz, Patrick |
description |
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. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018 |
dc.date.accessioned.fl_str_mv |
2020-07-08T13:09:52Z |
dc.date.available.fl_str_mv |
2020-07-08T13:09:52Z |
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info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Nature Communications. London, v. 9, p. -, 2018. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/54268 http://dx.doi.org/10.1038/s41467-017-02651-5 |
dc.identifier.issn.none.fl_str_mv |
2041-1723 |
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WOS000419658100005.pdf |
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10.1038/s41467-017-02651-5 |
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WOS:000419658100005 |
identifier_str_mv |
Nature Communications. London, v. 9, p. -, 2018. 2041-1723 WOS000419658100005.pdf 10.1038/s41467-017-02651-5 WOS:000419658100005 |
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https://repositorio.unifesp.br/handle/11600/54268 http://dx.doi.org/10.1038/s41467-017-02651-5 |
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Nature Publishing Group |
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Nature Publishing Group |
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