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Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome
BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidenti...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577832/ https://www.ncbi.nlm.nih.gov/pubmed/28861129 http://dx.doi.org/10.1186/s13148-017-0389-4 |
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author | Guastafierro, T. Bacalini, M. G. Marcoccia, A. Gentilini, D. Pisoni, S. Di Blasio, A. M. Corsi, A. Franceschi, C. Raimondo, D. Spanò, A. Garagnani, P. Bondanini, F. |
author_facet | Guastafierro, T. Bacalini, M. G. Marcoccia, A. Gentilini, D. Pisoni, S. Di Blasio, A. M. Corsi, A. Franceschi, C. Raimondo, D. Spanò, A. Garagnani, P. Bondanini, F. |
author_sort | Guastafierro, T. |
collection | PubMed |
description | BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. RESULTS: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. CONCLUSIONS: DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0389-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5577832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55778322017-08-31 Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome Guastafierro, T. Bacalini, M. G. Marcoccia, A. Gentilini, D. Pisoni, S. Di Blasio, A. M. Corsi, A. Franceschi, C. Raimondo, D. Spanò, A. Garagnani, P. Bondanini, F. Clin Epigenetics Short Report BACKGROUND: Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. RESULTS: To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. CONCLUSIONS: DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0389-4) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-30 /pmc/articles/PMC5577832/ /pubmed/28861129 http://dx.doi.org/10.1186/s13148-017-0389-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 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. |
spellingShingle | Short Report Guastafierro, T. Bacalini, M. G. Marcoccia, A. Gentilini, D. Pisoni, S. Di Blasio, A. M. Corsi, A. Franceschi, C. Raimondo, D. Spanò, A. Garagnani, P. Bondanini, F. Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome |
title | Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome |
title_full | Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome |
title_fullStr | Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome |
title_full_unstemmed | Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome |
title_short | Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome |
title_sort | genome-wide dna methylation analysis in blood cells from patients with werner syndrome |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577832/ https://www.ncbi.nlm.nih.gov/pubmed/28861129 http://dx.doi.org/10.1186/s13148-017-0389-4 |
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