Genome-wide impact of hydrogen peroxide on maintenance DNA methylation in replicating cells

Author:

Seddon Annika R.ORCID,Liau Yusmiati,Pace Paul E.,Miller Allison L.,Das Andrew B.,Kennedy Martin A.,Hampton Mark B.,Stevens Aaron J.

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 (H2O2). 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 H2O2. Results Sublethal H2O2 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 H2O2 can result in long-term alterations to DNA methylation patterns, providing a mechanism for environmental factors to have prolonged impact on gene expression.

Funder

Health Research Council of New Zealand

Canterbury Medical Research Foundation

Lotteries Heath Research Commission of New Zealand

Postgraduate Tassell Scholarship for Cancer Research.

Publisher

Springer Science and Business Media LLC

Subject

Genetics,Molecular Biology

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