Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape

Joseph G. Crompton, Manikandan Narayanan, Suresh Cuddapah, Rahul Roychoudhuri, Yun Ji, Wenjing Yang, Shashank J. Patel, Madhusudhanan Sukumar, Douglas C. Palmer, Weiqun Peng, Ena Wang, Francesco M. Marincola, Christopher A. Klebanoff, Keji Zhao, John S. Tsang, Luca Gattinoni, Nicholas P. Restifo

Research output: Contribution to journalArticle

35 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)502-513
Number of pages12
JournalCellular and Molecular Immunology
Issue number4
Publication statusPublished - 1 Jul 2016


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Crompton, J. G., Narayanan, M., Cuddapah, S., Roychoudhuri, R., Ji, Y., Yang, W., Patel, S. J., Sukumar, M., Palmer, D. C., Peng, W., Wang, E., Marincola, F. M., Klebanoff, C. A., Zhao, K., Tsang, J. S., Gattinoni, L., & Restifo, N. P. (2016). Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape. Cellular and Molecular Immunology, 13(4), 502-513.