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α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses
α-Synuclein (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. We used transgenic Drosophila and inducible SH-SY5Y neuroblastoma cells to investigate the e...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093762/ https://www.ncbi.nlm.nih.gov/pubmed/27808254 http://dx.doi.org/10.1038/srep36328 |
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author | Sugeno, Naoto Jäckel, Sandra Voigt, Aaron Wassouf, Zinah Schulze-Hentrich, Julia Kahle, Philipp J. |
author_facet | Sugeno, Naoto Jäckel, Sandra Voigt, Aaron Wassouf, Zinah Schulze-Hentrich, Julia Kahle, Philipp J. |
author_sort | Sugeno, Naoto |
collection | PubMed |
description | α-Synuclein (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. We used transgenic Drosophila and inducible SH-SY5Y neuroblastoma cells to investigate the effects of αS on chromatin with a particular focus on histone modifications. Overexpression of αS in male flies as well as in retinoic acid pre-treated neuroblastoma cells led to an elevation of histone H3K9 methylations, mostly mono- (H3K9me1) and di- (H3K9me2). The transient increase of H3K9 methylation in αS-induced SH-SY5Y cells was preceded by mRNA induction of the euchromatic histone lysine N-methyltransferase 2 (EHMT2). EHMT2 and H3K9me2 can function within the REST complex. Chromatin immunoprecipitation (ChIP) analyses of selected candidate, REST regulated genes showed significantly increased H3K9me2 promoter occupancy of genes encoding the L1CAM cell adhesion molecule and the synaptosomal-associated protein SNAP25, whose reduced expression levels were confirmed by RT-qPCR in αS induced cells. Treatment with EHMT inhibitor UNC0638 restored the mRNA levels of L1CAM and SNAP25. Thus, αS overexpression enhances H3K9 methylations via ΕΗΜΤ2 resulting in elevated H3K9me2 at the SNAP25 promoter, possibly affecting SNARE complex assembly and hence synaptic vesicle fusion events regulated by αS. |
format | Online Article Text |
id | pubmed-5093762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50937622016-11-10 α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses Sugeno, Naoto Jäckel, Sandra Voigt, Aaron Wassouf, Zinah Schulze-Hentrich, Julia Kahle, Philipp J. Sci Rep Article α-Synuclein (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. We used transgenic Drosophila and inducible SH-SY5Y neuroblastoma cells to investigate the effects of αS on chromatin with a particular focus on histone modifications. Overexpression of αS in male flies as well as in retinoic acid pre-treated neuroblastoma cells led to an elevation of histone H3K9 methylations, mostly mono- (H3K9me1) and di- (H3K9me2). The transient increase of H3K9 methylation in αS-induced SH-SY5Y cells was preceded by mRNA induction of the euchromatic histone lysine N-methyltransferase 2 (EHMT2). EHMT2 and H3K9me2 can function within the REST complex. Chromatin immunoprecipitation (ChIP) analyses of selected candidate, REST regulated genes showed significantly increased H3K9me2 promoter occupancy of genes encoding the L1CAM cell adhesion molecule and the synaptosomal-associated protein SNAP25, whose reduced expression levels were confirmed by RT-qPCR in αS induced cells. Treatment with EHMT inhibitor UNC0638 restored the mRNA levels of L1CAM and SNAP25. Thus, αS overexpression enhances H3K9 methylations via ΕΗΜΤ2 resulting in elevated H3K9me2 at the SNAP25 promoter, possibly affecting SNARE complex assembly and hence synaptic vesicle fusion events regulated by αS. Nature Publishing Group 2016-11-03 /pmc/articles/PMC5093762/ /pubmed/27808254 http://dx.doi.org/10.1038/srep36328 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Sugeno, Naoto Jäckel, Sandra Voigt, Aaron Wassouf, Zinah Schulze-Hentrich, Julia Kahle, Philipp J. α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses |
title | α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses |
title_full | α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses |
title_fullStr | α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses |
title_full_unstemmed | α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses |
title_short | α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses |
title_sort | α-synuclein enhances histone h3 lysine-9 dimethylation and h3k9me2-dependent transcriptional responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093762/ https://www.ncbi.nlm.nih.gov/pubmed/27808254 http://dx.doi.org/10.1038/srep36328 |
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