Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium

Autor: J. Ross Miller, Anke Liebert, Claire Fraser, Mariana Portovedo, Marco Aurélio Ramirez Vinolo, Raphaël Mattiuz, Payal Jain, Marc Veldhoen, Claudia Stellato, Juri Kazakevych, Patrick Varga-Weisz, Jérémy Denizot, Marina Célestine, Mia Mosavie, Hanneke Okkenhaug, Renan O. Corrêa
Přispěvatelé: The Babraham Institute [Cambridge, UK], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The Francis Crick Institute [London], University of Campinas (UNICAMP), School of Biological Sciences [Colchester], University of Essex, Laboratory of Lymphocyte Signalling and Development [Cambridge, UK] (Babraham Research Campus), Instituto de Medicina Molecular (iMM), Faculdade de Medicina [Lisboa], Universidade de Lisboa (ULISBOA)-Universidade de Lisboa (ULISBOA), Biotechnology and Biological Sciences Research Council (BBSRC) [BBS/E/B/000C0404], [BBS/E/B/000C0405], BBSRC-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/FAPESP-Brazil [BB/N013565/1, 2015/50379-1], Medical Research Council UK (MRC) [MR/N009398/1], Newton Advanced Fellowship from the Royal Society [NAF\R1\180116], Repositório da Universidade de Lisboa, ROSSI, Sabine, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Universidade de Lisboa = University of Lisbon (ULISBOA)-Universidade de Lisboa = University of Lisbon (ULISBOA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Division of Molecular Immunology, Biotechnology and Biological Sciences Research Council (BBSRC)BBS/E/B/000C0404BBS/E/B/000C0405Medical Research Council UK (MRC)MR/N009398/1BBSRC-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/FAPESP-Brazil BB/N013565/12015/50379-1Newton Advanced Fellowship from the Royal Society NAF\R1\180116
Jazyk: angličtina
Rok vydání: 2020
Předmět:
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
lcsh:QH426-470
Chromatin Remodeling Factor
[SDV.GEN] Life Sciences [q-bio]/Genetics
MESH: DNA Helicases / physiology
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Chromatin remodeling
Histones
MESH: Colitis / genetics
03 medical and health sciences
Mice
MESH: Regulatory Elements
Transcriptional
0302 clinical medicine
Gene expression
medicine
Animals
MESH: Microbiota
Regulatory Elements
Transcriptional
Colitis
Intestinal Mucosa
lcsh:QH301-705.5
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
030304 developmental biology
0303 health sciences
[SDV.GEN]Life Sciences [q-bio]/Genetics
Innate immune system
biology
Research
Microbiota
DNA Helicases
medicine.disease
Intestinal epithelium
MESH: Gene Expression Regulation
Cell biology
Chromatin
[SDV.BIO] Life Sciences [q-bio]/Biotechnology
lcsh:Genetics
Histone
lcsh:Biology (General)
Gene Expression Regulation
030220 oncology & carcinogenesis
biology.protein
MESH: Intestinal Mucosa / metabolism
Gene Deletion
Zdroj: Genome Biology
Genome Biology, BioMed Central, 2020, 21 (1), pp.1-20. ⟨10.1186/s13059-020-01976-7⟩
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Genome Biology, Vol 21, Iss 1, Pp 1-20 (2020)
Genome Biology, BioMed Central, 2020, 21 (1), ⟨10.1186/s13059-020-01976-7⟩
ISSN: 1465-6906
1474-760X
DOI: 10.1186/s13059-020-01976-7⟩
Popis: © The Author(s). 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Background: How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. Results: Specific deletion of Smarcad1 in the mouse intestinal epithelium leads to colitis resistance and substantial changes in gene expression, including a striking increase of expression of several genes linked to innate immunity. Absence of Smarcad1 leads to changes in chromatin accessibility and significant changes in histone H3K9me3 over many sites, including genes that are differentially regulated upon Smarcad1 deletion. We identify candidate members of the gut microbiome that elicit a Smarcad1-dependent colitis response, including members of the poorly understood TM7 phylum. Conclusions: Our study sheds light onto the role of the chromatin remodeling machinery in intestinal epithelial cells in the colitis response and shows how a highly conserved chromatin remodeling factor has a distinct role in anti-microbial defense. This work highlights the importance of the intestinal epithelium in the colitis response and the potential of microbial species as pharmacological and probiotic targets in the context of inflammatory diseases.
This work was supported by BBSRC Institute Strategic Programme Grants (BBS/E/B/000C0404, BBS/E/B/000C0405), a MRC project grant to PVW and MV (MR/N009398/1), a BBSRC-Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP-Brazil Pump-priming award (BB/N013565/1,FAPESP#2015/50379-1), and a Newton Advanced Fellowship from the Royal Society to MARV and PVW (NAF\R1\180116).
Databáze: OpenAIRE
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