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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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Kazakevych, Juri [1] ; Denizot, Jeremy [1, 2] ; Liebert, Anke [1, 3] ; Portovedo, Mariana [4] ; Mosavie, Mia [5] ; Jain, Payal [1] ; Stellato, Claudia [1] ; Fraser, Claire [1] ; Correa, Renan Oliveira [4] ; Celestine, Marina [1] ; Mattiuz, Raphael [1] ; Okkenhaug, Hanneke [6] ; Miller, J. Ross [1] ; Ramirez Vinolo, Marco Aurelio [4] ; Veldhoen, Marc [7, 8] ; Varga-Weisz, Patrick [5, 1]
Número total de Autores: 16
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] Francis Crick Inst, London NW1 1AT - England
[4] Inst Biol, Lab Immunoinflammat, UNICAMP, BR-13083862 Campinas - Brazil
[5] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex - England
[6] Babraham Inst, Imaging Facil, Cambridge CB22 3AT - England
[7] Babraham Inst, Lymphocyte Signalling & Dev, Cambridge CB22 3AT - England
[8] Univ Lisbon, Fac Med, Inst Med Mol Joao Lobo Antunes, P-1649028 Lisbon - Portugal
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: Genome Biology; v. 21, n. 1 MAR 11 2020.
Citações Web of Science: 0
Resumo

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. (AU)

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