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Published on: January 26, 2018
Arsenite alters global histone H3 methylation
Xue Zhou1, Hong Sun, Thomas P Ellen
1Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
Arsenic exposure alters key histone methylation marks, potentially driving cancer development. These epigenetic changes, affecting gene silencing and activation, may also influence DNA methylation patterns.
Area of Science:
- Environmental Toxicology
- Epigenetics
- Carcinogenesis
Background:
- Arsenic (As) is a known human carcinogen linked to epigenetic alterations like DNA methylation changes.
- The role of histone modifications in arsenic-induced carcinogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the impact of arsenic exposure on histone methylation patterns in human lung carcinoma cells.
- To elucidate the potential epigenetic mechanisms underlying arsenic's carcinogenic effects.
Main Methods:
- Exposure of A549 human lung carcinoma cells to inorganic trivalent arsenic (arsenite).
- Analysis of global histone methylation levels, including H3K9me2, H3K27me3, and H3K4me3.
- Quantification of histone methyltransferase G9a protein and mRNA levels.
Main Results:
- Arsenite exposure significantly altered histone methylation marks, increasing H3K9me2 and H3K4me3 while decreasing H3K27me3.
- The observed increase in H3K9me2 was associated with elevated G9a methyltransferase levels.
- Significant histone modification changes were noted even at low arsenite doses (0.1 microM).
Conclusions:
- Arsenic exposure induces specific histone methylation changes, impacting both gene silencing and activating marks.
- These histone modifications may contribute to arsenic-induced carcinogenesis, potentially by influencing DNA methylation.
- Further research is needed to explore the genomic localization of these epigenetic alterations.
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