Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development
Open Access
- 1 January 2013
- journal article
- Published by Springer Science and Business Media LLC in Genome Biology
- Vol. 14 (10), R108
- https://doi.org/10.1186/gb-2013-14-10-r108
Abstract
One in eleven people is affected by chronic kidney disease, a condition characterized by kidney fibrosis and progressive loss of kidney function. Epidemiological studies indicate that adverse intrauterine and postnatal environments have a long-lasting role in chronic kidney disease development. Epigenetic information represents a plausible carrier for mediating this programming effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and chronic kidney disease tubule samples obtained from patients show significant differences. We identify differentially methylated regions and validate these in a large replication dataset. The differentially methylated regions are rarely observed on promoters, but mostly overlap with putative enhancer regions, and they are enriched in consensus binding sequences for important renal transcription factors. This indicates their importance in gene expression regulation. A core set of genes that are known to be related to kidney fibrosis, including genes encoding collagens, show cytosine methylation changes correlating with downstream transcript levels. Our report raises the possibility that epigenetic dysregulation plays a role in chronic kidney disease development via influencing core pro-fibrotic pathways and can aid the development of novel biomarkers and future therapeutics.Keywords
This publication has 34 references indexed in Scilit:
- The accessible chromatin landscape of the human genomeNature, 2012
- Regulated Noise in the Epigenetic Landscape of Development and DiseaseCell, 2012
- ChromHMM: automating chromatin-state discovery and characterizationNature Methods, 2012
- Aberrant Epigenetic and Genetic Marks Are Seen in Myelodysplastic Leukocytes and Reveal Dock4 as a Candidate Pathogenic Gene on Chromosome 7qOnline Journal of Public Health Informatics, 2011
- RSAT 2011: regulatory sequence analysis toolsNucleic Acids Research, 2011
- Improved similarity scores for comparing motifsBioinformatics, 2011
- Fetal environment, epigenetics, and pediatric renal diseasePediatric Nephrology, 2010
- DNA methylation profiling using HpaII tiny fragment enrichment by ligation-mediated PCR (HELP)Methods, 2010
- Wilms Tumor Chromatin Profiles Highlight Stem Cell Properties and a Renal Developmental NetworkCell Stem Cell, 2010
- A pipeline for the quantitative analysis of CG dinucleotide methylation using mass spectrometryBioinformatics, 2009