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Methylmercury-induced DNA methylation-From epidemiological observations to experimental evidence. | LitMetric

AI Article Synopsis

  • * The researchers investigated the effects of MeHg on DNA methylation and gene expression in human SH-SY5Y cells, focusing on five genes identified in the earlier study, including MED31, which is crucial for fetal development.
  • * Findings showed increased methylation of MED31 with higher MeHg exposure, supporting previous epidemiological research, while also noting changes in GGH methylation that corresponded to its expression, emphasizing the need for experimental validation of associations found in observational studies. *

Article Abstract

Methylmercury (MeHg) is a developmental neurotoxicant, and one potential mechanism of MeHg toxicity is epigenetic dysregulation. In a recent meta-analysis of epigenome-wide association studies (EWAS), associations between prenatal MeHg exposure and DNA methylation at several genomic sites were identified in blood from newborns and children. While EWASs reveal human-relevant associations, experimental studies are required to validate the relationship between exposure and DNA methylation changes, and to assess if such changes have implications for gene expression. Herein, we studied DNA methylation and gene expression of five of the top genes identified in the EWAS meta-analysis, MED31, MRPL19, GGH, GRK1, and LYSMD3, upon MeHg exposure in human SH-SY5Y cells exposed to 8 or 40 nM of MeHg during differentiation, using bisulfite-pyrosequencing and qPCR, respectively. The concentrations were selected to cover the range of MeHg concentrations in cord blood (2-8.5 μg/L) observed in the cohorts included in the EWAS. Exposure to MeHg increased DNA methylation at MED31, a transcriptional regulator essential for fetal development. The results were in concordance with the epidemiological findings where more MED31 methylation was associated with higher concentrations of MeHg. Additionally, we found a non-significant decrease in DNA methylation at GGH, which corresponds to the direction of change observed in the EWAS, and a significant correlation of GGH methylation with its expression. In conclusion, this study corroborates some of the EWAS findings and puts forward candidate genes involved in MeHg's effects on the developing brain, thus highlighting the value of experimental validation of epidemiological association studies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513252PMC
http://dx.doi.org/10.3389/fgene.2022.993387DOI Listing

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