Project description:To better elucidate underlying mechanisms of circadian gene disruption on chronic kidney disease, we compared whole kidney transcriptome profiles between kidneys of WT and Bmal1 KO mice.
Project description:Genome wide DNA methylation profiling of urine and blood samples from patients with diabetic chronic kidney disease. The Illumina Infinium MethylationEPIC BeadChip kit was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included two urine and four buffy coat samples from adults with diabetic chronic kidney disease.
Project description:Epidemiological studies indicate that adverse intrauterine and postnatal environment has a long-lasting role in chronic kidney disease (CKD) development. Epigenetic information can represent a plausible carrier for mediating this programming effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and CKD tubule samples obtained from patients show significant differences. Cytosine methylation changes showed high concordance (98%) with a large (n=87) replication dataset. We rarely observed differentially methylated regions (DMR) on promoters. Histone modification-based kidney specific genome-wide gene regulatory region annotation maps (promoters, enhancers, transcribed and repressed regions) were generated. DMRs mostly overlapped with putative enhancer regions and were enriched in consensus binding sequences for important renal transcription factors, indicating their importance in gene expression regulation. A core set of genes, including transforming growth factors and collagens, showed cytosine methylation changes correlating with downstream transcript levels. Our report raises the possibility that epigenetic dysregulation plays a role in CKD development via influencing core profibrotic pathways. We used microarrays to detail the differences of gene expression of human tubule epithelial cells between chronic kidney disease and normal. We sought to decrease the cell type heterogeneity of kidney tissues to increase the resolution of expression profiles. To that end, microdissected human kidney tissue from both chronic kidney disease patient and normal are used for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Epidemiological studies indicate that adverse intrauterine and postnatal environment has a long-lasting role in chronic kidney disease (CKD) development. Epigenetic information can represent a plausible carrier for mediating this "programming" effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and CKD tubule samples obtained from patients show significant differences. We rarely observed differentially methylated regions (DMR) on promoters. Histone modification-based kidney specific genome-wide gene regulatory region annotation maps (promoters, enhancers, transcribed and repressed regions) were generated. DMRs mostly overlapped with putative enhancer regions and were enriched in consensus binding sequences for important renal transcription factors, indicating their importance in gene expression regulation. A core set of genes, including transforming growth factors and collagens, showed cytosine methylation changes correlating with downstream transcript levels. Our report raises the possibility that epigenetic dysregulation plays a role in CKD development via influencing core profibrotic pathways. HG18_HELP array We used custom-commercial array to detail the differences of methylation regions of human tubule epithelial cells between chronic kidney disease and normal. We sought to decrease the cell type heterogeneity of kidney tissues to increase the resolution of methylation profiles. To that end, microdissected human kidney tissue from both chronic kidney disease patient and normal are used for the HELP-assay (HpaII tiny fragment Enrichment by Ligation-mediated PCR) and hybridization on Roche NimbleGen microarrays.