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

Kazakevych, Juri and Denizot, Jérémy and Liebert, Anke and Portovedo, Mariana and Mosavie, Mia and Jain, Payal and Stellato, Claudia and Fraser, Claire and Corrêa, Renan Oliveira and Célestine, Marina and Mattiuz, Raphaël and Okkenhaug, Hanneke and Miller, J Ross and Vinolo, Marco Aurélio Ramirez and Veldhoen, Marc and Varga Weisz, Patrick (2020) 'Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium.' Genome Biology, 21 (1). ISSN 1474-760X

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Abstract

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.

Item Type: Article
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 27 Mar 2020 14:00
Last Modified: 27 Mar 2020 14:00
URI: http://repository.essex.ac.uk/id/eprint/27167

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