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Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development

2013; BioMed Central; Volume: 14; Issue: 10 Linguagem: Inglês

10.1186/gb-2013-14-10-r108

1474-760X

Yi-An Ko, Davoud Mohtat, Masako Suzuki, Ae Seo Deok Park, María C. Izquierdo, Sang Youb Han, Hyun Mi Kang, Han Si, Thomas H. Hostetter, James Pullman, Melissa Fazzari, Amit Verma, Deyou Zheng, John M. Greally, Katalin Suszták,

Genetic Syndromes and Imprinting

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.