1. Alteration of methylation status in the ATXN3 gene promoter region is linked to the SCA3/MJD.
- Author
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Wang C, Peng H, Li J, Ding D, Chen Z, Long Z, Peng Y, Zhou X, Ye W, Li K, Xu Q, Ai S, Song C, Weng L, Qiu R, Xia K, Tang B, and Jiang H
- Subjects
- Adult, Cells, Cultured, CpG Islands genetics, CpG Islands physiology, Disease Progression, Epigenesis, Genetic, Female, Humans, Male, Middle Aged, Trinucleotide Repeats genetics, Ataxin-3 genetics, DNA Methylation genetics, Genetic Association Studies, Genetic Predisposition to Disease genetics, Machado-Joseph Disease genetics, Promoter Regions, Genetic genetics, Repressor Proteins genetics
- Abstract
DNA methylation has been acknowledged as one of the key epigenetic mechanisms involved in the regulation of gene expression and genomic functions. Alteration of the DNA methylation level has been linked to modification of the disease progression and instability regulation of certain disease-causing repeats in neurodegenerative diseases. In this study, blood samples collected from spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patients versus control were used to explore the potential link of DNA methylation levels at ATXN3 gene promoter to the pathogenesis of SCA3/MJD. We found that the methylation levels in the ATXN3 promoter were significantly higher in SCA3/MJD patients relative to the controls. Furthermore, higher methylation levels were detected in the SCA3/MJD patients with earlier age at onset and the families with an intergenerational CAG repeats instability. In addition, the first CpG island of the ATXN3 promoter served as the main regulation region of DNA methylation. These findings suggested that an epigenetic change may contribute to the pathogenesis of the SCA3/MJD and provide potential therapeutic targets for CAG repeats-based diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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