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Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape
, G. Crompton Joseph, Cuddapah Suresh, Roychoudhuri Rahul, Ji Yun, Yang Wenjing, J. Patel Shashank, Sukumar Madhusudhanan, C. Palmer Douglas, Peng WeiqunShow More
Published in Springer Science and Business Media LLC
Volume: 13
Issue: 4
Pages: 502 - 513

To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory CD8+ T cells. Using a ChIP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 (H3K4me3) and H3 lysine 27 (H3K27me3) trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other CD8+ T-cell subsets. Taken together, our results suggest that CD8+ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have major implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory.

About the journal
JournalData powered by TypesetCellular & Molecular Immunology
PublisherData powered by TypesetSpringer Science and Business Media LLC
Open AccessNo