Genome-wide impact of hydrogen peroxide on maintenance DNA methylation in replicating cells
Annika R. Seddon, Yusmiati Liau, Paul E. Pace, Allison L. Miller, Andrew B. Das, Martin A. Kennedy, Mark B. Hampton, Aaron J. Stevens
Abstract
Abstract Background Environmental factors, such as oxidative stress, have the potential to modify the epigenetic landscape of cells. We have previously shown that DNA methyltransferase (DNMT) activity can be inhibited by sublethal doses of hydrogen peroxide (H 2 O 2 ). However, site-specific changes in DNA methylation and the reversibility of any changes have not been explored. Using bead chip array technology, differential methylation was assessed in Jurkat T-lymphoma cells following exposure to H 2 O 2 . Results Sublethal H 2 O 2 exposure was associated with an initial genome-wide decrease in DNA methylation in replicating cells, which was largely corrected 72 h later. However, some alterations were conserved through subsequent cycles of cell division. Significant changes to the variability of DNA methylation were also observed both globally and at the site-specific level. Conclusions This research indicates that increased exposure to H 2 O 2 can result in long-term alterations to DNA methylation patterns, providing a mechanism for environmental factors to have prolonged impact on gene expression.