Chromatin Methylation Abnormalities in Autosomal Dominant Polycystic Kidney Disease

Jing Xu; Jing Xu; Cheng Xue; Xiaodong Wang; Xiaodong Wang; Lei Zhang; Lei Zhang; Lei Zhang; Changlin Mei; Zhiguo Mao

doi:10.3389/fmed.2022.921631

Frontiers in Medicine (Jul 2022)

Chromatin Methylation Abnormalities in Autosomal Dominant Polycystic Kidney Disease

Jing Xu,
Jing Xu,
Cheng Xue,
Xiaodong Wang,
Xiaodong Wang,
Lei Zhang,
Lei Zhang,
Lei Zhang,
Changlin Mei,
Zhiguo Mao

Affiliations

Jing Xu: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
Jing Xu: State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
Cheng Xue: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
Xiaodong Wang: State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
Xiaodong Wang: School of Life Science and Technology, Shanghai Tech University, Shanghai, China
Lei Zhang: State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
Lei Zhang: School of Life Science and Technology, Shanghai Tech University, Shanghai, China
Lei Zhang: School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China
Changlin Mei: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
Zhiguo Mao: Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

DOI: https://doi.org/10.3389/fmed.2022.921631
Journal volume & issue: Vol. 9

Abstract

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease worldwide and is one of the major causes of end-stage renal disease. PKD1 and PKD2 are two genes that mainly contribute to the development and progression of ADPKD. The precise mechanism is not fully understood. In recent years, epigenetic modification has drawn increasing attention. Chromatin methylation is a very important category of PKD epigenetic changes and mostly involves DNA, histone, and RNA methylation. Genome hypomethylation and regional gene hypermethylation coexist in ADPKD. We found that the genomic DNA of ADPKD kidney tissues showed extensive demethylation by whole-genome bisulphite sequencing, while some regional DNA methylation from body fluids, such as blood and urine, can be used as diagnostic or prognostic biomarkers to predict PKD progression. Histone modifications construct the histone code mediated by histone methyltransferases and contribute to aberrant methylation changes in PKD. Considering the complexity of methylation abnormalities occurring in different regions and genes on the PKD epigenome, more specific therapy aiming to restore to the normal genome should lead to the development of epigenetic treatment.

Published in Frontiers in Medicine

ISSN: 2296-858X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Medicine (General)
Website: http://www.frontiersin.org/journals/medicine

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