title: Genome-wide DNA methylation analysis in renal ischemia reperfusion injury.
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<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<0.001 and P<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.
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Wujun
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, Affiliated Xi'an Central Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710003, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Nephrology, Affiliated Xi'an Central Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710003, PR China.
authors.forename: Sutong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: zhufeng0714@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: yuantian@xjtu.edu.cn.
authors.forename: Puxun
authors.initials: P
authors.lastname: Tian
mesh_terms: D000818:Animals; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D030541:Databases, Genetic; D049308:Dioxygenases / Q000235:genetics; D063990:Gene Ontology; D007668:Kidney / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D015427:Reperfusion Injury
chemical_list: D049308:Dioxygenases; D015254:DNA Modification Methylases
keywords: Bisulfite sequencing; DNA methylation; Ischemia reperfusion; Kidney; Mouse