The conserved DNMT1-dependent methylation regions in human cells are vulnerable to to neurotoxicant rotenone exposure
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ABSTRACT: Rotenone is a known neurotoxicant with both human and experimental data linking it to sporadic Parkinson's disease. We used RNAseq to identify global changes in gene expression and to identify vulnerable regions responsible to the rotenone treatment. Our goal was to determine if rotenone exposure alters chromatin mediated gene regulation mechanisms. We first explore their conservancy in the human genome. Our data show that our putative non-germline ASMs were in conserved regions of the human genome and located adjacent to genes vital for neuronal development and maturation. We next tested the hypothesized vulnerability of these regions by exposing human embryonic kidney cell HEK293 with the neurotoxicant rotenone for 24 h. Indeed,14 genes adjacent to our identified regions were differentially expressed from RNA-sequencing. We analyzed the base-resolution methylation patterns of the predicted non-germline ASMs at two neurological genes, HCN2 and NEFM, with potential to increase the risk of neurodegeneration. Both regions were significantly hypomethylated in response to rotenone.
ORGANISM(S): Homo sapiens
PROVIDER: GSE147617 | GEO | 2021/03/26
REPOSITORIES: GEO
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