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Series GSE135335 Query DataSets for GSE135335
Status Public on Jun 19, 2020
Title Epigenomic analysis of Parkinson’s disease neurons identifies TET2 loss as neuroprotective [PD_hMeDIP_Seq]
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Epigenetic control of enhancers is centrally involved in modifying neuronal functions and may contribute to Parkinson's disease (PD) pathogenesis. Here, we comprehensively profile DNA methylation at enhancers genome-wide in neurons of 57 PD patients and 48 healthy individuals. There is a widespread increase in cytosine modifications at enhancers in PD neurons, which is partly due to elevated hydroxymethylation levels. Epigenetic dysregulation of enhancers in PD converge on transcriptional abnormalities affecting neuronal signaling and immune activation pathways. In particular, PD patients exhibit an epigenetic and transcriptional upregulation of TET2, a master-regulator of cytosine modification status. TET2 inactivation in a neuronal cell line enriches for cytosine modification changes that are reciprocal to those observed in PD neurons. Furthermore, Tet2 inactivation in mice fully prevents dopaminergic neuronal loss in the substantia nigra induced by prior inflammation. Tet2 loss in mice also attenuates transcriptional immune responses to an inflammatory trigger. Thus, widespread epigenetic dysregulation of enhancers in PD neurons may, in part, be mediated by increased TET2 expression. Decreased Tet2 activity is neuroprotective, in vivo, and may be a novel therapeutic target for PD.
Overall design In order to determine the extent to which 5-hydroxymethylcytosine contributes to the epigenetically misregulated enhancers involved in PD, we used hMeDIP-seq to profile hydroxymethylation genome-wide in neurons of PD patients and healthy control individuals (44 individuals: 21 PD, 23 controls).
Contributor(s) Marshall L, Killinger B, Li P, Ensink E, Cui W, Li K, Gordevicius J, Weiland M, Jovinge S, Labrie V
Citation(s) 32807949
Submission date Aug 02, 2019
Last update date Sep 18, 2020
Contact name Lee Marshall
Phone 616 920 9824
Organization name Van Andel Research Institute
Department Center for Neurodegenerative Science
Lab Viviane Labrie
Street address 333 Bostwick Ave NE
City Grand Rapids
State/province MI
ZIP/Postal code 49503
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (45)
GSM4007931 CTRL_166_PD_hMeDIP_Seq
GSM4007932 CTRL_149_PD_hMeDIP_Seq
GSM4007933 CTRL_194_PD_hMeDIP_Seq
This SubSeries is part of SuperSeries:
GSE136010 Epigenomic analysis of Parkinson's disease neurons identifies TET2 loss as neuroprotective
BioProject PRJNA558780
SRA SRP217499

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Supplementary file Size Download File type/resource
GSE135335_RAW.tar 539.1 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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