Cargando…

Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke

To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2)...

Descripción completa

Detalles Bibliográficos
Autores principales: Deng, Guo-Xiong, Xu, Ning, Huang, Qi, Tan, Jin-Yue, Zhang, Zhao, Li, Xian-Feng, Wei, Jin-Ru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781986/
https://www.ncbi.nlm.nih.gov/pubmed/31527307
http://dx.doi.org/10.18632/aging.102278
_version_ 1783457474113699840
author Deng, Guo-Xiong
Xu, Ning
Huang, Qi
Tan, Jin-Yue
Zhang, Zhao
Li, Xian-Feng
Wei, Jin-Ru
author_facet Deng, Guo-Xiong
Xu, Ning
Huang, Qi
Tan, Jin-Yue
Zhang, Zhao
Li, Xian-Feng
Wei, Jin-Ru
author_sort Deng, Guo-Xiong
collection PubMed
description To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group (P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis.
format Online
Article
Text
id pubmed-6781986
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Impact Journals
record_format MEDLINE/PubMed
spelling pubmed-67819862019-10-16 Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke Deng, Guo-Xiong Xu, Ning Huang, Qi Tan, Jin-Yue Zhang, Zhao Li, Xian-Feng Wei, Jin-Ru Aging (Albany NY) Research Paper To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group (P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis. Impact Journals 2019-09-17 /pmc/articles/PMC6781986/ /pubmed/31527307 http://dx.doi.org/10.18632/aging.102278 Text en Copyright © 2019 Deng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Deng, Guo-Xiong
Xu, Ning
Huang, Qi
Tan, Jin-Yue
Zhang, Zhao
Li, Xian-Feng
Wei, Jin-Ru
Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke
title Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke
title_full Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke
title_fullStr Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke
title_full_unstemmed Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke
title_short Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke
title_sort association between promoter dna methylation and gene expression in the pathogenesis of ischemic stroke
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781986/
https://www.ncbi.nlm.nih.gov/pubmed/31527307
http://dx.doi.org/10.18632/aging.102278
work_keys_str_mv AT dengguoxiong associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke
AT xuning associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke
AT huangqi associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke
AT tanjinyue associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke
AT zhangzhao associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke
AT lixianfeng associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke
AT weijinru associationbetweenpromoterdnamethylationandgeneexpressioninthepathogenesisofischemicstroke