Abstract
BackgroundEnvironmental 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.ResultsSublethal 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.ConclusionsThis 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.
Highlights
Environmental factors, such as oxidative stress, have the potential to modify the epigenetic landscape of cells
Immune cells such as neutrophils and macrophages generate a range of reactive oxygen species following NADPH oxidase (NOX) activation, many of which are cell permeable, and contribute to oxidative stress during inflammation [11, 20, 21]. H2O2 and Seddon et al Epigenetics & Chromatin (2021) 14:17 myeloperoxidase-derived oxidants produced by immune cells can oxidize redox-sensitive thiol proteins and methionine [22,23,24]
Cultured Jurkat T-lymphoma cells were synchronized with a thymidine block to maximize the number undergoing DNA synthesis at the time of exposure to oxidative stress
Summary
Environmental factors, such as oxidative stress, have the potential to modify the epigenetic landscape of cells. Epigenetic modification of chromatin provides a mechanistic basis through which environmental stimuli can modulate gene expression Epigenetic marks, such as methylation of cytosine and histone modifications, are utilized during development to generate a wide range of cellular phenotypes from the same DNA code. Ageing, smoking, radiation and xenobiotic metabolism can result in increased H2O2 in biological systems [13,14,15,16,17,18,19] Immune cells such as neutrophils and macrophages generate a range of reactive oxygen species following NADPH oxidase (NOX) activation, many of which are cell permeable, and contribute to oxidative stress during inflammation [11, 20, 21]. Methionine is a precursor of the methyl donor S-adenosyl-methionine (SAM)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.