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| Status |
Public on Oct 13, 2021 |
| Title |
Mitochondrial Dysfunction Induces Epigenetic Dysregulation by H3K27 Hyperacetylation to Perturb Active Enhancers in Parkinson’s Disease Models |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
We aim to explore the predominant mitochondrial dysfunctions in PD, with a focus on how altering the histone code contributes to PD pathogenesis. We employ a multidisciplinary approach to convincingly demonstrate that neurotoxicant exposure- and genetic mutation-driven mitochondrial dysfunction share a common mechanism of epigenetic dysregulation. Under both scenarios, lysine 27 acetylation of likely variant H3.2 (H3.2K27ac) increased in dopaminergic neuronal models of PD, thereby opening that region to active enhancer activity via H3K27 hyperacetylation. These vulnerable epigenomic loci represent potential transcription factor motifs for PD pathogenesis. Our results reveal an exciting axis of ‘exposure/mutation-mitochondrial dysfunction-metabolism-H3K27ac-transcriptome’ for PD pathogenesis. Collectively, the novel mechanistic insights presented here interlinks mitochondrial dysfunction to epigenetic transcriptional regulation in dopaminergic degeneration as well as offer potential new epigenetic intervention strategies for PD.
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| Overall design |
We performed genome-wide ChIP-Seq characterization of H3K27ac as well as transcriptome profiling in dopaminergic neurons whose mitochondria had been impaired either by exposure to a neurotoxic pesticide or by genetic modifications.
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| Contributor(s) |
Huang M, Lou D, Charli A, Kong D, Jin H, Anantharam V, Kanthasamy A, Wang Z, Kanthasamy AG |
| Citation(s) |
34494552 |
| |
| Submission date |
Nov 18, 2019 |
| Last update date |
Oct 14, 2021 |
| Contact name |
Zhibin Wang |
| E-mail(s) |
zwang47@jhu.edu
|
| Organization name |
Johns Hopkins University
|
| Department |
Environmental Health and Engineering
|
| Street address |
615 N Wolf Steet
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24688 |
HiSeq X Ten (Rattus norvegicus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA590131 |
| SRA |
SRP230384 |
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