Histone architecture of stem-cell memory T cells reveals progressive remodeling of epigenetic landscape after activation of CD8 T cells

To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed after T cell activation, we investigated the genomic landscape of histone modifications in antigen-experienced 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 distinct subsets of CD8+ T cells-nave, stem cell memory, central memory, and effector memory-to gain insight into how histone architecture is remodeled during the differentiation of activated T cells. 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 regions associated with T cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified stem cell memory T cell from other antigen-experienced CD8+ T cell subsets. Taken together, our results suggest that antigen-experienced T cells may undergo chromatin remodeling in a progressive fashion that may have implications for our understanding of peripheral T cell ontogeny and the formation of immunological memory.

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Crompton JG, Narayanan M, Cuddapah S, Roychoudhuri R, Ji Y, Yang W, Patel SJ, Sukumar M, Palmer DC, Peng W, Wang E, Marincola FM, Klebanoff CA, Zhao K, Tsang JS, Gattinoni L, Restifo NP