NOS2 and S -nitrosothiol signaling induces DNA hypomethylation and LINE-1 retrotransposon expression
| العنوان: | NOS2 and S -nitrosothiol signaling induces DNA hypomethylation and LINE-1 retrotransposon expression |
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| المؤلفون: | Christopher H. Switzer, Hyun-Ju Cho, Thomas R. Eykyn, Paul Lavender, Philip Eaton |
| المصدر: | Proceedings of the National Academy of Sciences. 119 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | Significance Nitric oxide is a multifaceted signaling molecule that affects multiple pathways and cellular systems. Here, we report that inducible nitric oxide synthase expression, which is strongly correlated with inflammation and poor outcomes in patients with cancer, substantially alters DNA methylation to regulate cellular plasticity. Our data connect inflammation mechanistically with stress signals, DNA demethylation, and genotoxic retrotransposon expression. Passive DNA demethylation occurs during conditions of reduced DNA (cytosine-5)–methyltransferase 1 (DNMT1) activity; however, the cellular pathways that control passive demethylation are not clear. Our results show that sustained cellular stress signals result in DNMT1 protein loss and DNA hypomethylation, similar to DNMT1 inhibition by 5-azacytidine. This implies that chronic inflammation drives cellular transformation via DNA hypomethylation and retrotransposon activation. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::fe4bda255607f243ce3998f70d6966ebTest https://doi.org/10.1073/pnas.2200022119Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........fe4bda255607f243ce3998f70d6966eb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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