Genome-wide DNA methylation analysis in renal ischemia reperfusion injury

Renal ischemia reperfusion injury (IRI) is frequently encountered after kidney transplantation and is a leading cause of acute renal failure. Aberrant gene expression and epigenetic regulation occur during the pathophysiology of IRI. In this study, we used reduced representation bisulfite sequencing...

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Veröffentlicht in:Gene 2017-04, Vol.610, p.32-43
Hauptverfasser: Zhao, Yanlong, Ding, Chenguang, Xue, Wujun, Ding, Xiaoming, Zheng, Jin, Gao, Yi, Xia, Xinxin, Li, Sutong, Liu, Jing, Han, Feng, Zhu, Feng, Tian, Puxun
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container_issue
container_start_page 32
container_title Gene
container_volume 610
creator Zhao, Yanlong
Ding, Chenguang
Xue, Wujun
Ding, Xiaoming
Zheng, Jin
Gao, Yi
Xia, Xinxin
Li, Sutong
Liu, Jing
Han, Feng
Zhu, Feng
Tian, Puxun
description Renal ischemia reperfusion injury (IRI) is frequently encountered after kidney transplantation and is a leading cause of acute renal failure. Aberrant gene expression and epigenetic regulation occur during the pathophysiology of IRI. In this study, we used reduced representation bisulfite sequencing to identify the DNA methylome of renal tissues during IRI and the sham-operated tissues in C57BL/6. The methylation status of approximately 1.29 million CpGs located in an average of 11554 CpG islands and 17113 promoters in genome was determined. Compared with sham-operated kidney, both acute and chronic IRI significantly decreased the genome-wide methylation level (1.1–1.8%) and the CpG methylation level in the promoter (0.4–0.5%), CpG island (0.5–1.3%), exon (1.3–1.9%), and intron (0.8–1.1%; all P
doi_str_mv 10.1016/j.gene.2017.02.005
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Aberrant gene expression and epigenetic regulation occur during the pathophysiology of IRI. In this study, we used reduced representation bisulfite sequencing to identify the DNA methylome of renal tissues during IRI and the sham-operated tissues in C57BL/6. The methylation status of approximately 1.29 million CpGs located in an average of 11554 CpG islands and 17113 promoters in genome was determined. Compared with sham-operated kidney, both acute and chronic IRI significantly decreased the genome-wide methylation level (1.1–1.8%) and the CpG methylation level in the promoter (0.4–0.5%), CpG island (0.5–1.3%), exon (1.3–1.9%), and intron (0.8–1.1%; all P&lt;10−153). The promoters of 200, 191, and 79 genes were differentially methylated in the renal tissues at 24h, 7days, and at both the time points after IRI, respectively. Among the 79 genes, which were consistently epigenetically regulated at two time points, 18 genes (22.8%) showed differential expression after IRI in a previous study of renal expression. We validated the promoter methylation status and expression of five out of the 18 genes, including 2700049A03Rik, Ccr9, Fgd2, Pfkfb3, and Sdc4 in an independent renal tissue cohort. We found that all the five genes exhibited altered methylation of promoter (P=0.009–0.0001) following renal injury. The promoter methylation of 2700049A03Rik and Ccr9 was negatively correlated with their mRNA expression in renal tissues (P&lt;0.001 and P&lt;0.0001, respectively). Our study not only demonstrated a genome-wide DNA methylation pattern in the IR-injured renal tissue for the first time, but also indicated that the regulation of promoter methylation is an important mechanism underlying persistent alteration of gene expression. •Renal IRI decreased the genome-wide DNA methylation level.•The promoters of genes were differentially methylated in the IRI renal.•The modification of promoter methylation regulated IRI renal gene expression.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2017.02.005</identifier><identifier>PMID: 28189760</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Bisulfite sequencing ; Databases, Genetic ; Dioxygenases - genetics ; DNA Methylation ; DNA Modification Methylases - genetics ; Gene Ontology ; Ischemia reperfusion ; Kidney ; Kidney - injuries ; Kidney - metabolism ; Kidney - pathology ; Kidney - physiology ; Male ; Mice ; Mouse ; Promoter Regions, Genetic ; Reperfusion Injury</subject><ispartof>Gene, 2017-04, Vol.610, p.32-43</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. 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Among the 79 genes, which were consistently epigenetically regulated at two time points, 18 genes (22.8%) showed differential expression after IRI in a previous study of renal expression. We validated the promoter methylation status and expression of five out of the 18 genes, including 2700049A03Rik, Ccr9, Fgd2, Pfkfb3, and Sdc4 in an independent renal tissue cohort. We found that all the five genes exhibited altered methylation of promoter (P=0.009–0.0001) following renal injury. The promoter methylation of 2700049A03Rik and Ccr9 was negatively correlated with their mRNA expression in renal tissues (P&lt;0.001 and P&lt;0.0001, respectively). Our study not only demonstrated a genome-wide DNA methylation pattern in the IR-injured renal tissue for the first time, but also indicated that the regulation of promoter methylation is an important mechanism underlying persistent alteration of gene expression. •Renal IRI decreased the genome-wide DNA methylation level.•The promoters of genes were differentially methylated in the IRI renal.•The modification of promoter methylation regulated IRI renal gene expression.</description><subject>Animals</subject><subject>Bisulfite sequencing</subject><subject>Databases, Genetic</subject><subject>Dioxygenases - genetics</subject><subject>DNA Methylation</subject><subject>DNA Modification Methylases - genetics</subject><subject>Gene Ontology</subject><subject>Ischemia reperfusion</subject><subject>Kidney</subject><subject>Kidney - injuries</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mouse</subject><subject>Promoter Regions, Genetic</subject><subject>Reperfusion Injury</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLFOwzAQhi0EoqXwAgwoI0uC7TSOLbFUBUqlChaYLde5UEeJU-wElLfHUQsjt5xO-u7X3YfQNcEJwYTdVckHWEgoJnmCaYJxdoKmhOcixjjlp2iK05zHhBAxQRfeVzhUltFzNKGccJEzPEXrFdi2gfjbFBA9vCyiBrrdUKvOtDZSVtWDNz4yNnIQhsh4vYPGqDDuwZW9HzFjq94Nl-isVLWHq2Ofofenx7flc7x5Xa2Xi02s55R2MRSsANBbpljBeUYKAtm8LDOhBWWCgdAEp4JxSnORZ0oLRVWqGaQpS7Eq5-kM3R5y96797MF3sglXQV0rC23vJeEsFyGYsoDSA6pd672DUu6daZQbJMFyVCgrOSqUo0KJqQx-wtLNMb_fNlD8rfw6C8D9AYDw5ZcBJ702YDUUxoHuZNGa__J_AJREgkY</recordid><startdate>20170430</startdate><enddate>20170430</enddate><creator>Zhao, Yanlong</creator><creator>Ding, Chenguang</creator><creator>Xue, Wujun</creator><creator>Ding, Xiaoming</creator><creator>Zheng, Jin</creator><creator>Gao, Yi</creator><creator>Xia, Xinxin</creator><creator>Li, Sutong</creator><creator>Liu, Jing</creator><creator>Han, Feng</creator><creator>Zhu, Feng</creator><creator>Tian, Puxun</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170430</creationdate><title>Genome-wide DNA methylation analysis in renal ischemia reperfusion injury</title><author>Zhao, Yanlong ; Ding, Chenguang ; Xue, Wujun ; Ding, Xiaoming ; Zheng, Jin ; Gao, Yi ; Xia, Xinxin ; Li, Sutong ; Liu, Jing ; Han, Feng ; Zhu, Feng ; Tian, Puxun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-ed6deecb6a6d8851d1e54ff59c92696e9c103968227975ac9a2a3c6e33630af43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Bisulfite sequencing</topic><topic>Databases, Genetic</topic><topic>Dioxygenases - genetics</topic><topic>DNA Methylation</topic><topic>DNA Modification Methylases - genetics</topic><topic>Gene Ontology</topic><topic>Ischemia reperfusion</topic><topic>Kidney</topic><topic>Kidney - injuries</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney - physiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mouse</topic><topic>Promoter Regions, Genetic</topic><topic>Reperfusion Injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Yanlong</creatorcontrib><creatorcontrib>Ding, Chenguang</creatorcontrib><creatorcontrib>Xue, Wujun</creatorcontrib><creatorcontrib>Ding, Xiaoming</creatorcontrib><creatorcontrib>Zheng, Jin</creatorcontrib><creatorcontrib>Gao, Yi</creatorcontrib><creatorcontrib>Xia, Xinxin</creatorcontrib><creatorcontrib>Li, Sutong</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Han, Feng</creatorcontrib><creatorcontrib>Zhu, Feng</creatorcontrib><creatorcontrib>Tian, Puxun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Yanlong</au><au>Ding, Chenguang</au><au>Xue, Wujun</au><au>Ding, Xiaoming</au><au>Zheng, Jin</au><au>Gao, Yi</au><au>Xia, Xinxin</au><au>Li, Sutong</au><au>Liu, Jing</au><au>Han, Feng</au><au>Zhu, Feng</au><au>Tian, Puxun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide DNA methylation analysis in renal ischemia reperfusion injury</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2017-04-30</date><risdate>2017</risdate><volume>610</volume><spage>32</spage><epage>43</epage><pages>32-43</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>Renal ischemia reperfusion injury (IRI) is frequently encountered after kidney transplantation and is a leading cause of acute renal failure. Aberrant gene expression and epigenetic regulation occur during the pathophysiology of IRI. In this study, we used reduced representation bisulfite sequencing to identify the DNA methylome of renal tissues during IRI and the sham-operated tissues in C57BL/6. The methylation status of approximately 1.29 million CpGs located in an average of 11554 CpG islands and 17113 promoters in genome was determined. Compared with sham-operated kidney, both acute and chronic IRI significantly decreased the genome-wide methylation level (1.1–1.8%) and the CpG methylation level in the promoter (0.4–0.5%), CpG island (0.5–1.3%), exon (1.3–1.9%), and intron (0.8–1.1%; all P&lt;10−153). The promoters of 200, 191, and 79 genes were differentially methylated in the renal tissues at 24h, 7days, and at both the time points after IRI, respectively. Among the 79 genes, which were consistently epigenetically regulated at two time points, 18 genes (22.8%) showed differential expression after IRI in a previous study of renal expression. We validated the promoter methylation status and expression of five out of the 18 genes, including 2700049A03Rik, Ccr9, Fgd2, Pfkfb3, and Sdc4 in an independent renal tissue cohort. We found that all the five genes exhibited altered methylation of promoter (P=0.009–0.0001) following renal injury. The promoter methylation of 2700049A03Rik and Ccr9 was negatively correlated with their mRNA expression in renal tissues (P&lt;0.001 and P&lt;0.0001, respectively). Our study not only demonstrated a genome-wide DNA methylation pattern in the IR-injured renal tissue for the first time, but also indicated that the regulation of promoter methylation is an important mechanism underlying persistent alteration of gene expression. •Renal IRI decreased the genome-wide DNA methylation level.•The promoters of genes were differentially methylated in the IRI renal.•The modification of promoter methylation regulated IRI renal gene expression.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28189760</pmid><doi>10.1016/j.gene.2017.02.005</doi><tpages>12</tpages></addata></record>
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subjects Animals
Bisulfite sequencing
Databases, Genetic
Dioxygenases - genetics
DNA Methylation
DNA Modification Methylases - genetics
Gene Ontology
Ischemia reperfusion
Kidney
Kidney - injuries
Kidney - metabolism
Kidney - pathology
Kidney - physiology
Male
Mice
Mouse
Promoter Regions, Genetic
Reperfusion Injury
title Genome-wide DNA methylation analysis in renal ischemia reperfusion injury
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