Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures

Cielo, D.; Galatola, M.; Fernández Jiménez, Nora; De Leo, L.; García Etxebarria, Koldo; Loganes, C.; Tommasini, A.; Not, T.; Auricchio, Renata; Greco, Luigi; Bilbao Catalá, José Ramón

dc.contributor.author	Cielo, D.
dc.contributor.author	Galatola, M.
dc.contributor.author	Fernández Jiménez, Nora
dc.contributor.author	De Leo, L.
dc.contributor.author	García Etxebarria, Koldo
dc.contributor.author	Loganes, C.
dc.contributor.author	Tommasini, A.
dc.contributor.author	Not, T.
dc.contributor.author	Auricchio, Renata
dc.contributor.author	Greco, Luigi
dc.contributor.author	Bilbao Catalá, José Ramón
dc.date.accessioned	2020-02-24T09:24:16Z
dc.date.available	2020-02-24T09:24:16Z
dc.date.issued	2019-07-10
dc.identifier.citation	Scientific Reports 9 : (2019) // Article ID 10020	es_ES
dc.identifier.issn	2045-2322
dc.identifier.uri	http://hdl.handle.net/10810/41404
dc.description.abstract	By GWAS studies on celiac disease, gene expression was studied at the level of the whole intestinal mucosa, composed by two different compartments: epithelium and lamina propria. Our aim is to analyse the gene-expression and DNA methylation of candidate genes in each of these compartments. Epithelium was separated from lamina propria in biopsies of CeD patients and CTRs using magnetic beads. Gene-expression was analysed by RT-PC; methylation analysis required bisulfite conversion and NGS. Reverse modulation of gene-expression and methylation in the same cellular compartment was observed for the IL21 and SH2B3 genes in CeD patients relative to CTRs. Bioinformatics analysis highlighted the regulatory elements in the genomic region of SH2B3 that altered methylation levels. The cREL and TNFAIP3 genes showed methylation patterns that were significantly different between CeD patients and CTRs. In CeD, the genes linked to inflammatory processes are up-regulated, whereas the genes involved in the cell adhesion/ integrity of the intestinal barrier are down-regulated. These findings suggest a correlation between gene-expression and methylation profile for the IL21 and SH2B3 genes. We identified a "gene-expression phenotype" of CeD and showed that the abnormal response to dietary antigens in CeD might be related not to abnormalities of gene structure but to the regulation of molecular pathways.	es_ES
dc.description.sponsorship	This work was funded by the FC-Grant2013. Programma di mobilita nell'ambito delle reti di eccellenza POR Campania FSE 2007-2013 Asse V. The authors thank the European Laboratory for Food-induced Disease (ELFID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	es_ES
dc.language.iso	eng	es_ES
dc.publisher	Nature Publishing Group	es_ES
dc.rights	info:eu-repo/semantics/openAccess	es_ES
dc.rights.uri	http://creativecommons.org/licenses/by/3.0/es/	*
dc.subject	adapter protein	es_ES
dc.subject	endothelial-cells	es_ES
dc.subject	self-renewal	es_ES
dc.subject	lnk	es_ES
dc.subject	immune	es_ES
dc.subject	inhibition	es_ES
dc.subject	diagnosis	es_ES
dc.subject	variants	es_ES
dc.subject	cloning	es_ES
dc.subject	signal	es_ES
dc.title	Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures	es_ES
dc.type	info:eu-repo/semantics/article	es_ES
dc.rights.holder	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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.	es_ES
dc.rights.holder	Atribución 3.0 España	*
dc.relation.publisherversion	https://www.nature.com/articles/s41598-019-46468-2#rightslink	es_ES
dc.identifier.doi	10.1038/s41598-019-46468-2
dc.departamentoes	Genética, antropología física y fisiología animal	es_ES
dc.departamentoeu	Genetika,antropologia fisikoa eta animalien fisiologia	es_ES

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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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

Except where otherwise noted, this item's license is described as 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.