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过氧化氢对复制细胞中维持 DNA 甲基化的全基因组影响。

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

机构信息

Department of Pathology and Biomedical Science, University of Otago, PO Box 4345, Christchurch, 8140, New Zealand.

出版信息

Epigenetics Chromatin. 2021 Mar 24;14(1):17. doi: 10.1186/s13072-021-00388-6.

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 (HO). 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 HO.

RESULTS

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

摘要

背景

环境因素,如氧化应激,有可能改变细胞的表观遗传景观。我们之前已经表明,亚致死剂量的过氧化氢 (HO) 可以抑制 DNA 甲基转移酶 (DNMT) 活性。然而,DNA 甲基化的特异性变化以及任何变化的可逆性尚未得到探索。使用珠子芯片阵列技术,在 HO 暴露后评估 Jurkat T 淋巴细胞瘤细胞中的差异甲基化。

结果

亚致死 HO 暴露与复制细胞中 DNA 甲基化的全基因组初始减少相关,这在 72 小时后基本得到纠正。然而,一些改变在随后的细胞分裂周期中得到了保留。在全局和特定部位水平上,还观察到 DNA 甲基化变异性的显著变化。

结论

这项研究表明,增加 HO 的暴露会导致 DNA 甲基化模式的长期改变,为环境因素对基因表达产生长期影响提供了一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b74/7992848/f7aee2b6037b/13072_2021_388_Fig1_HTML.jpg

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