title: Alteration of methylation status in the ATXN3 gene promoter region is linked to the SCA3/MJD.
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.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Jiada
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Ding
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Sanxi
authors.initials: S
authors.lastname: Ai
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Weng
authors.affiliation: School of Information Science and Engineering, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, P. R. China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China; State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, P. R. China. Electronic address: jianghong73868@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000067699:Ataxin-3 / Q000235:genetics*; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3
keywords: ATXN3 promoter; Anticipation; DNA methylation; DNMT1; Dynamic mutation; SCA3/MJD