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 investiga...

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Bibliographic Details
Published in:	Epigenetics Vol. 19; no. 1; p. 2367385
Main Authors:	Seddon, Annika R, Damiano, Olivia M, Hampton, Mark B, Stevens, Aaron J
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 01-12-2024 Taylor & Francis Group
Subjects:	ADAM10 Protein - genetics ADAM10 Protein - metabolism CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Proliferation CpG Islands differentiation DNA Methylation Epigenesis, Genetic Humans inflammation Lymphocyte Activation Membrane Proteins - genetics oxidants redox biology T-cell epigenetics redox biology differentiation T-cell epigenetics proliferation inflammation CD3/CD28 DNA methylation oxidants
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Summary:	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 , , and . While many changes had modest effect sizes, approximately 120 CpGs exhibited a log FC 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1559-2294 1559-2308 1559-2308
DOI:	10.1080/15592294.2024.2367385