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Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress
Oxidative stress is a common feature of inflammation-driven cancers, and it promotes genomic instability and aggressive tumour phenotypes. It is known that oxidative stress transiently modulates gene expression through the oxidation of transcription factors and associated regulatory proteins. Neutro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896486/ https://www.ncbi.nlm.nih.gov/pubmed/36106794 http://dx.doi.org/10.1093/hmg/ddac232 |
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author | Seddon, Annika R Das, Andrew B Hampton, Mark B Stevens, Aaron J |
author_facet | Seddon, Annika R Das, Andrew B Hampton, Mark B Stevens, Aaron J |
author_sort | Seddon, Annika R |
collection | PubMed |
description | Oxidative stress is a common feature of inflammation-driven cancers, and it promotes genomic instability and aggressive tumour phenotypes. It is known that oxidative stress transiently modulates gene expression through the oxidation of transcription factors and associated regulatory proteins. Neutrophils are our most abundant white blood cells and accumulate at sites of infection and inflammation. Activated neutrophils produce hypochlorous acid and chloramines, which can disrupt DNA methylation by oxidizing methionine. The goal of the current study was to determine whether chloramine exposure results in sequence-specific modifications in DNA methylation that enable long-term alterations in transcriptional output. Proliferating Jurkat T-lymphoma cells were exposed to sublethal doses of glycine chloramine and differential methylation patterns were compared using Illumina EPIC 850 K bead chip arrays. There was a substantial genome-wide decrease in methylation 4 h after exposure that correlated with altered RNA expression for 24 and 48 h, indicating sustained impacts on exposed cells. A large proportion of the most significant differentially methylated CpG sites were situated towards chromosomal ends, suggesting that these regions are most susceptible to inhibition of maintenance DNA methylation. This may contribute to epigenetic instability of chromosomal ends in rapidly dividing cells, with potential implications for the regulation of telomere length and cellular longevity. |
format | Online Article Text |
id | pubmed-9896486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98964862023-02-06 Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress Seddon, Annika R Das, Andrew B Hampton, Mark B Stevens, Aaron J Hum Mol Genet Original Article Oxidative stress is a common feature of inflammation-driven cancers, and it promotes genomic instability and aggressive tumour phenotypes. It is known that oxidative stress transiently modulates gene expression through the oxidation of transcription factors and associated regulatory proteins. Neutrophils are our most abundant white blood cells and accumulate at sites of infection and inflammation. Activated neutrophils produce hypochlorous acid and chloramines, which can disrupt DNA methylation by oxidizing methionine. The goal of the current study was to determine whether chloramine exposure results in sequence-specific modifications in DNA methylation that enable long-term alterations in transcriptional output. Proliferating Jurkat T-lymphoma cells were exposed to sublethal doses of glycine chloramine and differential methylation patterns were compared using Illumina EPIC 850 K bead chip arrays. There was a substantial genome-wide decrease in methylation 4 h after exposure that correlated with altered RNA expression for 24 and 48 h, indicating sustained impacts on exposed cells. A large proportion of the most significant differentially methylated CpG sites were situated towards chromosomal ends, suggesting that these regions are most susceptible to inhibition of maintenance DNA methylation. This may contribute to epigenetic instability of chromosomal ends in rapidly dividing cells, with potential implications for the regulation of telomere length and cellular longevity. Oxford University Press 2022-09-15 /pmc/articles/PMC9896486/ /pubmed/36106794 http://dx.doi.org/10.1093/hmg/ddac232 Text en © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Seddon, Annika R Das, Andrew B Hampton, Mark B Stevens, Aaron J Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress |
title | Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress |
title_full | Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress |
title_fullStr | Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress |
title_full_unstemmed | Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress |
title_short | Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress |
title_sort | site-specific decreases in dna methylation in replicating cells following exposure to oxidative stress |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896486/ https://www.ncbi.nlm.nih.gov/pubmed/36106794 http://dx.doi.org/10.1093/hmg/ddac232 |
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