The DNA methylation profile of activated human natural killer cells

Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation chang...

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Vydáno v:Epigenetics Ročník 11; číslo 5; s. 363 - 380
Hlavní autoři: Wiencke, John. K., Butler, Rondi, Hsuang, George, Eliot, Melissa, Kim, Stephanie, Sepulveda, Manuel A., Siegel, Derick, Houseman, E. Andres, Kelsey, Karl T.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Taylor & Francis 03.05.2016
Témata:
Adaptive Immunity - genetics
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - immunology
Blood Donors
CpG Islands - genetics
Differentially methylated regions
digital PCR
DNA - genetics
DNA - immunology
DNA methylation
DNA Methylation - genetics
DNA Methylation - immunology
Epigenesis, Genetic - genetics
Epigenesis, Genetic - immunology
Genome-Wide Association Study
Homeodomain Proteins - genetics
Homeodomain Proteins - immunology
Humans
innate immunity
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Lymphocyte Activation - genetics
NK cells
NKp46
Promoter Regions, Genetic
Research Paper
DNA methylation
NK cells
Differentially methylated regions
NKp46
digital PCR
innate immunity
ISSN:1559-2294, 1559-2308
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Shrnutí:Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states.
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Supplemental material data for this article can be accessed on the publisher's website.
ISSN:1559-2294
1559-2308
DOI:10.1080/15592294.2016.1163454