Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells

Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8 T cells, we performed genome-wide analysis of DNA methylation, histone mark...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2017-01, Vol.198 (2), p.937-949
Main Authors: Rodriguez, Ramon M, Suarez-Alvarez, Beatriz, Lavín, José L, Mosén-Ansorena, David, Baragaño Raneros, Aroa, Márquez-Kisinousky, Leonardo, Aransay, Ana M, Lopez-Larrea, Carlos
Format: Article
Language:English
Subjects:
Acetylation
Blotting, Western
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell activation
Cell Differentiation - genetics
Cell Differentiation - immunology
Cell Separation
Chromatin Immunoprecipitation
Demethylation
DNA Methylation
Epigenesis, Genetic
Epigenetics
Flow Cytometry
Gene expression
Gene Expression Profiling
Gene Expression Regulation - genetics
Gene Expression Regulation - immunology
Genes
Genomes
Histone H3
Humans
Immunologic Memory - genetics
Immunologic Memory - immunology
Immunological memory
Innate immunity
Killer cell immunoglobulin-like receptors
KIR2DL4 protein
Landscape
Lymphocytes
Lymphocytes T
Lysine
Memory cells
Methylation
Natural killer cells
Oligonucleotide Array Sequence Analysis
Potassium channels (inwardly-rectifying)
Real-Time Polymerase Chain Reaction
Regulators
Transcription
Transcription, Genetic
Transcriptome
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Summary:Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8 T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8 T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8 T cell maintenance and T cell terminal differentiation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1601102