Epigenetics DNA methylation in the core ataxin-2 gene promoter: novel physiological and pathological implications

摘要: Pathogenic CAG (cytosine-adenine-guanine) expansions beyond certain thresholds in the ataxin-2 (ATXN2) gene cause spinocerebellar ataxia type 2 (SCA2) and were shown to contribute Parkinson disease, amyotrophic lateral sclerosis frontotemporal lobar degeneration. Regulation of ATXN2 expression function protein product are not known. SCA2 exhibits an inverse correlation between size repeat age at disease onset. However, a wide range onset typically observed, with number alone explaining only partly this variability. In study, we explored hypothesis that levels could be controlled by DNA methylation derangement control may lead escalation severity influencing We found CpG human promoter is associated pathogenic patients. Different pedigree without intergenerational instability caused anticipation family. also influenced homozygotes SCA3 conclusion, our study points novel regulatory mechanism involving epigenetic event resulting differential course