Annika R Seddon, Olivia M Damiano, Mark B Hampton, Aaron J Stevens
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Relatively few of the differentially methylated CpGs occurred along adjacent gene regions. The exceptions were seven differentially methylated gene regions, with the Human T cell Receptor Alpha Joining Genes demonstrating consistent methylation change over a 3kb window. We also investigated whether an inflammatory environment could alter DNA methylation during activation, with proliferating cells exposed to the oxidant glycine chloramine. No substantial differential methylation was observed in this context. The temporal perspective of early activation adds depth to the evolving field of epigenetic immunology, offering insights with implications for therapeutic innovation and expanding our understanding of epigenetic modulation in immune function.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2367385"},"PeriodicalIF":2.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195465/pdf/","citationCount":"0","resultStr":"{\"title\":\"Widespread genomic <i>de novo</i> DNA methylation occurs following CD8<sup>+</sup> T cell activation and proliferation.\",\"authors\":\"Annika R Seddon, Olivia M Damiano, Mark B Hampton, Aaron J Stevens\",\"doi\":\"10.1080/15592294.2024.2367385\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This research investigates the intricate dynamics of DNA methylation in the hours following CD8+ T cell activation, during a critical yet understudied temporal window. 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We also investigated whether an inflammatory environment could alter DNA methylation during activation, with proliferating cells exposed to the oxidant glycine chloramine. No substantial differential methylation was observed in this context. The temporal perspective of early activation adds depth to the evolving field of epigenetic immunology, offering insights with implications for therapeutic innovation and expanding our understanding of epigenetic modulation in immune function.</p>\",\"PeriodicalId\":11767,\"journal\":{\"name\":\"Epigenetics\",\"volume\":\"19 1\",\"pages\":\"2367385\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195465/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epigenetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/15592294.2024.2367385\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2024.2367385","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/20 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
这项研究调查了 DNA 甲基化在 CD8+ T 细胞活化后数小时内的复杂动态,这是一个关键的时间窗口,但尚未得到充分研究。DNA 甲基化是一种表观遗传修饰,是调控基因表达和引导免疫反应的核心。我们的研究跨越了激活后的 96 小时,揭示了全局和特定位点甲基化变化的细微差别。我们在整个基因组中发现了 15,626 个具有显著差异的甲基化 CpGs,其中最显著的变化发生在 ADAM10、ICA1 和 LAPTM5 基因中。虽然许多变化的效应大小不大,但约有 120 个 CpGs 的 log2FC 超过了 1.5,其中受影响最大的是细胞活化和增殖途径。在相邻基因区域发生不同甲基化的 CpGs 相对较少。例外情况是有七个不同的甲基化基因区域,其中人类 T 细胞受体 Alpha 连接基因在 3kb 窗口内显示出一致的甲基化变化。我们还研究了炎症环境是否会改变活化过程中的 DNA 甲基化,增殖细胞暴露于氧化剂甘氨酸氯胺中。在这种情况下,没有观察到实质性的甲基化差异。早期活化的时间视角为不断发展的表观遗传免疫学领域增加了深度,提供了对治疗创新有意义的见解,并扩展了我们对免疫功能中表观遗传调控的理解。
Widespread genomic de novo DNA methylation occurs following CD8+ T cell activation and proliferation.
This research investigates the intricate dynamics of DNA methylation in the hours following CD8+ T cell activation, during a critical yet understudied temporal window. DNA methylation is an epigenetic modification central to regulation of gene expression and directing immune responses. Our investigation spanned 96-h post-activation and unveils a nuanced tapestry of global and site-specific methylation changes. We identified 15,626 significant differentially methylated CpGs spread across the genome, with the most significant changes occurring within the genes ADAM10, ICA1, and LAPTM5. While many changes had modest effect sizes, approximately 120 CpGs exhibited a log2FC above 1.5, with cell activation and proliferation pathways the most affected. Relatively few of the differentially methylated CpGs occurred along adjacent gene regions. The exceptions were seven differentially methylated gene regions, with the Human T cell Receptor Alpha Joining Genes demonstrating consistent methylation change over a 3kb window. We also investigated whether an inflammatory environment could alter DNA methylation during activation, with proliferating cells exposed to the oxidant glycine chloramine. No substantial differential methylation was observed in this context. The temporal perspective of early activation adds depth to the evolving field of epigenetic immunology, offering insights with implications for therapeutic innovation and expanding our understanding of epigenetic modulation in immune function.
期刊介绍:
Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed.
Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to):
DNA methylation
Nucleosome positioning and modification
Gene silencing
Imprinting
Nuclear reprogramming
Chromatin remodeling
Non-coding RNA
Non-histone chromosomal elements
Dosage compensation
Nuclear organization
Epigenetic therapy and diagnostics
Nutrition and environmental epigenetics
Cancer epigenetics
Neuroepigenetics