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• W3089738353 endingPage "128486" @default.
• W3089738353 startingPage "128486" @default.
• W3089738353 abstract "Lead (Pb) is a commonly found heavy metal due to its historical applications. Recent studies have associated early-life Pb exposure with the onset of various neurodegenerative disease. The molecular mechanisms of Pb conferring long-term neurotoxicity, however, is yet to be elucidated. In this study, we explored the persistency of alteration in epigenetic marks that arise from exposure to low dose of Pb using a combination of image-based and gene expression analysis. Using SH-SY5Y as a model cell line, we observed significant alterations in global 5-methycytosine (5 mC) and histone 3 lysine 27 tri-methylation (H3K27me3) and histone 3 lysine 9 tri-methylation (H3K9me3) levels in a dose-dependent manner immediately after Pb exposure. The changes are partially associated with alterations in epigenetic enzyme expression levels. Long term culturing (14 days) after cease of exposure revealed persistent changes in 5 mC, partial recovery in H3K9me3 and overcompensation in H3K27me3 levels. The observed alterations in H3K9me3 and H3K27me3 are reversed after neuronal differentiation, while reduction in 5 mC levels are amplified with significant changes in patterns as identified via texture clustering analysis. Moreover, correlation analysis demonstrates a strong positive correlation between trends of 5 mC alteration after differentiation and neuronal morphology. Collectively, our results suggest that exposure to low dose of Pb prior to differentiation can result in persistent epigenome alterations that can potentially be responsible for the observed phenotypic changes. Our work reveals that Pb induced changes in epigenetic repressive marks can persist through neuron differentiation, which provides a plausible mechanism underlying long-term neurotoxicity associated with developmental Pb-exposure." @default.
• W3089738353 created "2020-10-08" @default.
• W3089738353 creator A5003262339 @default.
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• W3089738353 date "2021-02-01" @default.
• W3089738353 modified "2023-10-15" @default.
• W3089738353 title "Low dose lead exposure induces alterations on heterochromatin hallmarks persisting through SH-SY5Y cell differentiation" @default.
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• W3089738353 doi "https://doi.org/10.1016/j.chemosphere.2020.128486" @default.
• W3089738353 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33032221" @default.
• W3089738353 hasPublicationYear "2021" @default.
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