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

Yi An Ko, Davoud Mohtat, Masako Suzuki, Ae S D Park, Maria C. Izquierdo, Sang Y. Han, Hyun M. Kang, Han Si, Thomas Hostetter, James M. Pullman, Melissa Fazzari, Amit K. Verma, Deyou Zheng, John M. Greally, Katalin Susztak

Research output: Contribution to journalArticle

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Abstract

Background: 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.Results: 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.Conclusions: 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.

Original languageEnglish (US)
Article numberR108
JournalGenome Biology
Volume14
Issue number10
DOIs
StatePublished - Oct 7 2013

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cytosine
Cytosine
methylation
kidney diseases
fibrosis
Chronic Renal Insufficiency
Methylation
Fibrosis
kidneys
Kidney
gene
Epigenomics
epigenetics
Genes
genes
Kidney Tubules
development aid
collagen
Consensus Sequence
gene expression regulation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development. / Ko, Yi An; Mohtat, Davoud; Suzuki, Masako; Park, Ae S D; Izquierdo, Maria C.; Han, Sang Y.; Kang, Hyun M.; Si, Han; Hostetter, Thomas; Pullman, James M.; Fazzari, Melissa; Verma, Amit K.; Zheng, Deyou; Greally, John M.; Susztak, Katalin.

In: Genome Biology, Vol. 14, No. 10, R108, 07.10.2013.

Research output: Contribution to journalArticle

Ko, Yi An ; Mohtat, Davoud ; Suzuki, Masako ; Park, Ae S D ; Izquierdo, Maria C. ; Han, Sang Y. ; Kang, Hyun M. ; Si, Han ; Hostetter, Thomas ; Pullman, James M. ; Fazzari, Melissa ; Verma, Amit K. ; Zheng, Deyou ; Greally, John M. ; Susztak, Katalin. / Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development. In: Genome Biology. 2013 ; Vol. 14, No. 10.
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AU - Si, Han

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AU - Susztak, Katalin

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