GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE140524 Query DataSets for GSE140524
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
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.
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.
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
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
Platforms (1)
GPL24688 HiSeq X Ten (Rattus norvegicus)
Samples (24)
GSM4173689 Crispr TFAM RNAseq rep1
GSM4173690 Crispr TFAM RNAseq rep2
GSM4173691 Crispr TFAM RNAseq rep3
BioProject PRJNA590131
SRA SRP230384

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
GSE140524_N27_Ctrl_vs_Rote_rpkm.txt.gz 434.7 Kb (ftp)(http) TXT
GSE140524_N27_Ctrl_vs_TFAMKO_rpkm.txt.gz 433.3 Kb (ftp)(http) TXT
GSE140524_RAW.tar 2.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap