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Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development
Open accessAbstract
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.
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In a genome-wide DNA methylation study of human kidney tubules, several genes associated with kidney fibrosis are characterized by methylation changes and alterations of downstream transcript levels in chronic kidney disease samples compared with controls.
“In a genome-wide DNA methylation study of human kidney tubules, several genes that are associated with kidney fibrosis were characterized by methylation changes and alterations of downstream transcript levels in CKD samples compared with controls197.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [197]
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Epigenetic instability of imprinted genes in human cancers
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Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
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“Moreover, all published studies to date of the DNA methylation in fibrotic diseases have been limited to studying restricted subsets of genes or to the use of microarrays that lack genome-wide coverage [17–23].”
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“Using complex statistical analytical methods we identified 4751 DMRs when control and CKD kidney samples were compared [43].”
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“7,12,31 In the identified 94 genes, only 5 had promoter hypermethylation in UUO that was suppressed by 5-Aza, namely A930004D18Rik, 6330409D20Rik, Pds5b, Hoxa5, and AI428936 (Figure 3a).”
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Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes
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InfluentialEpigenetics in Kidney Transplantation
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Metadata
- Authors
- Ko, Y.-A., Mohtat, D., Suzuki, M., Park, A. S. D., Izquierdo, M. C., Han, S. Y., Kang, H. M., Si, H., Hostetter, T., Pullman, J. M., Fazzari, M., Verma, A., Zheng, D., Greally, J. M., & Susztak, K.
- Affiliations
- University of Pennsylvania (US)
- Albert Einstein College of Medicine (US)
- Case Western Reserve University (US)
- Montefiore Medical Center (US)
- Corresponding author
- Greally, John M
- ORCID
- Venue
- Genome Biology
- Published
- 2013-12-10
- Volume
- 14
- Issue
- 10
- Pages
- R108-R108
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC4053753
- OpenAlex
- W2130816592
- Cited by
- 225
- References
- 35
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 19 · 2023: 9 · 2022: 10 · 2021: 14 · 2020: 16 · 2019: 24 · 2018: 29 · 2017: 20 · 2016: 16 · 2015: 30 · 2014: 16 · 2013: 3
- FWCI
- 9.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087635)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- cytosine methylation, renal fibrosis, chronic kidney disease, differentially methylated regions, enhancers, epigenetic dysregulation, collagen genes, gene expression regulation, developmental programming, biomarkers
- MeSH terms
- Aged, Base Sequence, Binding Sites, Cytosine, Enhancer Elements, Genetic, Fibrosis, Gene Expression Regulation, Humans, Kidney, Middle Aged, Transcription Factors, Transcription, Genetic, Reproducibility of Results, Cluster Analysis, Case-Control Studies, DNA Methylation, Gene Expression Profiling, Renal Insufficiency, Chronic, Gene Regulatory Networks, Position-Specific Scoring Matrices, Nucleotide Motifs
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