Session Information
Date: Tuesday, June 6, 2017
Session Title: Parkinson's Disease: Pathophysiology
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: To explore the nuclear function of alpha-synuclein (αS).
Background: αS is a protein linked to Parkinson’s disease (PD) and related neurodegenerative disorders. It is mostly localized within synapses, but αS has also been suggested to play a role in the nucleus. The aim of this study is to explore epigenetic events through αS.
Methods: Histone proteins, extracted from αS transgenic Drosophila and αS inducible SH-SY5Y neuroblastoma cells, were separated by SDS-PAGE, then histone marks were analyzed by western blotting. To determine the level of histone lysine methyltransferase (HMT) and histone lysine demethylase (KDM), mRNA levels were measured by RT-PCR. Chromatin immunoprecipitation was performed by standard protocol using H3K9me2 and REST antibodies. Target genes were amplified by specific primer pairs.
Results: Overexpression of αS in male flies as well as in retinoic acid pre-treated neuroblastoma cells led to an elevation of histone H3K9 methylation, mostly mono- (H3K9me1) and di- (H3K9me2), which mean transcriptional repression. The transient increase of H3K9 methylation in SY5Y cells was slightly preceded by an induction of the euchromatic histone lysine N-methyltransferase 2 (EHMT2). Pharmacological inhibition of EHMT2 reduced the H3K9 methylations. EHMT2 and H3K9me2 can function within the REST complex. H3K9me2 chromatin immunoprecipitation (ChIP) survey of REST regulated genes showed significantly increased promoter occupancy of the synaptosomal-associated protein SNAP25 and cell adhesion molecule L1CAM genes after αS induction. Transcripts and protein levels of SNAP25 were also decreased.
Conclusions: αS overexpression enhances the histone modifications H3K9me1 and H3K9me2, likely involving EHMT2 known to catalyze these histone modifications. While, H3K9me2 strongly appears at the SNAP25 promoter, possibly affecting SNARE complex assembly and hence synaptic function regulated by αS.
References: Sugeno N, Jackel S, Voigt A, Wassouf Z, Schulze-Hentrich J, Kahle PJ (2016) alpha-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses. Scientific reports 6: 36328
To cite this abstract in AMA style:
N. Sugeno, S. Jäckel, A. Voigt, T. Hasegawa, P. Kahle. Alpha-synuclein enhances histone H3 lysine-9 dimethylation [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/alpha-synuclein-enhances-histone-h3-lysine-9-dimethylation/. Accessed June 15, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-enhances-histone-h3-lysine-9-dimethylation/