Alpha-synuclein overexpression induces epigenomic dysregulation of glutamate signaling and locomotor pathways
2022 | journal article. A publication with affiliation to the University of Göttingen.
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Alpha-synuclein overexpression induces epigenomic dysregulation of glutamate signaling and locomotor pathways
Schaffner, S. L.; Wassouf, Z.; Lazaro, D. F.; Xylaki, M.; Gladish, N.; Lin, D. T. S. & MacIsaac, J. et al. (2022)
Human Molecular Genetics, art. ddac104. DOI: https://doi.org/10.1093/hmg/ddac104
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Details
- Authors
- Schaffner, Samantha L.; Wassouf, Zinah; Lazaro, Diana F.; Xylaki, Mary; Gladish, Nicole; Lin, David T. S.; MacIsaac, Julia; Ramadori, Katia; Hentrich, Thomas; Schulze-Hentrich, Julia M.; Kobor, Michael S.
- Abstract
- Abstract Parkinson’s disease (PD) is a neurological disorder with complex interindividual etiology that is becoming increasingly prevalent worldwide. Elevated alpha-synuclein levels can increase risk of PD and may influence epigenetic regulation of PD pathways. Here, we report genome-wide DNA methylation and hydroxymethylation alterations associated with overexpression of two PD-linked alpha-synuclein variants (wild-type and A30P) in LUHMES cells differentiated to dopaminergic neurons. Alpha-synuclein altered DNA methylation at thousands of CpGs and DNA hydroxymethylation at hundreds of CpGs in both genotypes, primarily in locomotor behavior and glutamate signaling pathway genes. In some cases, epigenetic changes were associated with transcription. SMITE network analysis incorporating H3K4me1 ChIP-seq to score DNA methylation and hydroxymethylation changes across promoters, enhancers, and gene bodies confirmed epigenetic and transcriptional deregulation of glutamate signaling modules in both genotypes. Our results identify distinct and shared impacts of alpha-synuclein variants on the epigenome, and associate alpha-synuclein with the epigenetic etiology of PD.
- Issue Date
- 2022
- Journal
- Human Molecular Genetics
- Project
- EXC 2067: Multiscale Bioimaging
SFB 1286: Quantitative Synaptologie
SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration - Working Group
- RG Outeiro (Experimental Neurodegeneration)
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Language
- English