| Literature DB >> 27789799 |
Debattama R Sen1,2, James Kaminski3, R Anthony Barnitz1, Makoto Kurachi4,5, Ulrike Gerdemann1, Kathleen B Yates1, Hsiao-Wei Tsao1, Jernej Godec1,2, Martin W LaFleur1,2, Flavian D Brown1,2, Pierre Tonnerre6, Raymond T Chung6, Damien C Tully7, Todd M Allen7, Nicole Frahm8, Georg M Lauer6, E John Wherry4,5, Nir Yosef9,7,10, W Nicholas Haining11,12,13.
Abstract
Exhausted T cells in cancer and chronic viral infection express distinctive patterns of genes, including sustained expression of programmed cell death protein 1 (PD-1). However, the regulation of gene expression in exhausted T cells is poorly understood. Here, we define the accessible chromatin landscape in exhausted CD8+ T cells and show that it is distinct from functional memory CD8+ T cells. Exhausted CD8+ T cells in humans and a mouse model of chronic viral infection acquire a state-specific epigenetic landscape organized into functional modules of enhancers. Genome editing shows that PD-1 expression is regulated in part by an exhaustion-specific enhancer that contains essential RAR, T-bet, and Sox3 motifs. Functional enhancer maps may offer targets for genome editing that alter gene expression preferentially in exhausted CD8+ T cells.Entities:
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Year: 2016 PMID： 27789799 PMCID： PMC5497589 DOI： 10.1126/science.aae0491
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728