Title: Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.
Authors: Crompton, Joseph G; Narayanan, Manikandan; Cuddapah, Suresh; Roychoudhuri, Rahul; Ji, Yun; Yang, Wenjing; Patel, Shashank J; Sukumar, Madhusudhanan; Palmer, Douglas C; Peng, Weiqun; Wang, Ena; Marincola, Francesco M; Klebanoff, Christopher A; Zhao, Keji; Tsang, John S; Gattinoni, Luca; Restifo, Nicholas P
Published In Cell Mol Immunol, (2016 07)
Abstract: 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.
PubMed ID: 25914936
MeSH Terms: Animals; CD8-Positive T-Lymphocytes/cytology*; CD8-Positive T-Lymphocytes/metabolism*; Cell Lineage/genetics*; Cell Lineage/immunology*; Chromatin Assembly and Disassembly/genetics; Enhancer Elements, Genetic/genetics; Epigenesis, Genetic*; Gene Expression Profiling; Histones/metabolism; Immunologic Memory/genetics; Lymphocyte Subsets/metabolism; Methylation; Mice, Inbred C57BL; Promoter Regions, Genetic/genetics; Protein Processing, Post-Translational