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Series GSE135750 Query DataSets for GSE135750
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
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.
Overall design Chromatin immunoprecipitation (ChIP) was used to identify active enhancers and promoters in the healthy human appendix (n = 3 individuals)
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
Phone 6162345547
Organization name Van Andel Research Institute
Department Center for Neurodegenerative Science
Lab Labrie lab
Street address 333 Bostwick Ave N.E.
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (9)
GSM4027447 8_ChIP: input1
GSM4027448 8_ChIP: input2
GSM4027449 8_ChIP: input3
This SubSeries is part of SuperSeries:
GSE135751 Epigenetic inactivation of the autophagy-lysosomal system in the Parkinson’s disease appendix
BioProject PRJNA559920
SRA SRP218163

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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