Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Genome Biology |
| Online Access: | http://link.springer.com/article/10.1186/s13059-020-01976-7 |
| _version_ | 1828307897336987648 |
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| author | Juri Kazakevych Jérémy Denizot Anke Liebert Mariana Portovedo Mia Mosavie Payal Jain Claudia Stellato Claire Fraser Renan Oliveira Corrêa Marina Célestine Raphaël Mattiuz Hanneke Okkenhaug J. Ross Miller Marco Aurélio Ramirez Vinolo Marc Veldhoen Patrick Varga-Weisz |
| author_facet | Juri Kazakevych Jérémy Denizot Anke Liebert Mariana Portovedo Mia Mosavie Payal Jain Claudia Stellato Claire Fraser Renan Oliveira Corrêa Marina Célestine Raphaël Mattiuz Hanneke Okkenhaug J. Ross Miller Marco Aurélio Ramirez Vinolo Marc Veldhoen Patrick Varga-Weisz |
| author_sort | Juri Kazakevych |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:04:39Z |
| format | Article |
| id | doaj.art-bc150fa4d28746ba8b0f4a6c65280385 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-04-13T15:04:39Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-bc150fa4d28746ba8b0f4a6c652803852022-12-22T02:42:11ZengBMCGenome Biology1474-760X2020-03-0121112010.1186/s13059-020-01976-7Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epitheliumJuri Kazakevych0Jérémy Denizot1Anke Liebert2Mariana Portovedo3Mia Mosavie4Payal Jain5Claudia Stellato6Claire Fraser7Renan Oliveira Corrêa8Marina Célestine9Raphaël Mattiuz10Hanneke Okkenhaug11J. Ross Miller12Marco Aurélio Ramirez Vinolo13Marc Veldhoen14Patrick Varga-Weisz15Nuclear Dynamics, Babraham InstituteNuclear Dynamics, Babraham InstituteNuclear Dynamics, Babraham InstituteLaboratory of Immunoinflammation, Institute of Biology, UNICAMPSchool of Biological Sciences, University of EssexNuclear Dynamics, Babraham InstituteNuclear Dynamics, Babraham InstituteNuclear Dynamics, Babraham InstituteLaboratory of Immunoinflammation, Institute of Biology, UNICAMPNuclear Dynamics, Babraham InstituteNuclear Dynamics, Babraham InstituteImaging Facility, Babraham InstituteNuclear Dynamics, Babraham InstituteLaboratory of Immunoinflammation, Institute of Biology, UNICAMPLymphocyte Signalling and Development, Babraham InstituteNuclear Dynamics, Babraham InstituteAbstract 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.http://link.springer.com/article/10.1186/s13059-020-01976-7 |
| spellingShingle | Juri Kazakevych Jérémy Denizot Anke Liebert Mariana Portovedo Mia Mosavie Payal Jain Claudia Stellato Claire Fraser Renan Oliveira Corrêa Marina Célestine Raphaël Mattiuz Hanneke Okkenhaug J. Ross Miller Marco Aurélio Ramirez Vinolo Marc Veldhoen Patrick Varga-Weisz Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium Genome Biology |
| title | Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium |
| title_full | Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium |
| title_fullStr | Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium |
| title_full_unstemmed | Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium |
| title_short | Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium |
| title_sort | smarcad1 mediates microbiota induced inflammation in mouse and coordinates gene expression in the intestinal epithelium |
| url | http://link.springer.com/article/10.1186/s13059-020-01976-7 |
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