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| Status |
Public on Mar 01, 2021 |
| Title |
Epigenetic inactivation of the autophagy-lysosomal system in the Parkinson’s disease appendix (8: ChIP) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
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| Overall design |
Chromatin immunoprecipitation (ChIP) was used to identify active enhancers and promoters in the healthy human appendix (n = 3 individuals)
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| Contributor(s) |
Gordevicius J, Li P, Marshall L, Killinger B, Lang S, Ensink E, Kuhn N, Cui W, Maroof N, Vega I, Manfredsson F, Britschgi M, Labrie V |
| Citation(s) |
33406628, 34446734 |
| Submission date |
Aug 12, 2019 |
| Last update date |
Sep 29, 2021 |
| Contact name |
Peipei Li |
| E-mail(s) |
Lipeipei0611@gmail.com
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| Phone |
6162345547
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| Organization name |
Van Andel Research Institute
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| Department |
Center for Neurodegenerative Science
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| Lab |
Labrie lab
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| Street address |
333 Bostwick Ave N.E.
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| City |
Grand Rapids |
| State/province |
MI |
| ZIP/Postal code |
49503 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE135751 |
Epigenetic inactivation of the autophagy-lysosomal system in the Parkinson’s disease appendix |
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| Relations |
| BioProject |
PRJNA559920 |
| SRA |
SRP218163 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135750_ACvsinput_peaks.narrowPeak_IDR0.05_conservative_final.bed.gz |
322.3 Kb |
(ftp)(http) |
BED |
| GSE135750_ACvsinput_peaks.txt.gz |
4.6 Mb |
(ftp)(http) |
TXT |
| GSE135750_MEvsinput_peaks.narrowPeak_IDR0.05_conservative_final.bed.gz |
457.4 Kb |
(ftp)(http) |
BED |
| GSE135750_MEvsinput_peaks.txt.gz |
7.3 Mb |
(ftp)(http) |
TXT |
| GSE135750_RAW.tar |
24.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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