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Immunity. 2016 Dec 20;45(6):1327-1340. doi: 10.1016/j.immuni.2016.10.028. Epub 2016 Dec 6.

Dynamic Changes in Chromatin Accessibility Occur in CD8+ T Cells Responding to Viral Infection.

Author information

1
Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA.
2
Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA; Computational Oncoepigenomics Group, Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
3
Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA; Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92037, USA. Electronic address: arao@lji.org.

Abstract

In response to acute infection, naive CD8+ T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8+ T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8+ T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state. Regions differentially accessible between functional subsets in vivo were enriched for binding sites of transcription factors known to regulate these subsets, including E2A, BATF, IRF4, T-bet, and TCF1. Exhaustion-specific accessible regions were enriched for consensus binding sites for NFAT and Nr4a family members, indicating that chronic stimulation confers a unique accessibility profile on exhausted cells.

PMID:
27939672
PMCID:
PMC5214519
DOI:
10.1016/j.immuni.2016.10.028
[Indexed for MEDLINE]
Free PMC Article

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