title: Dynamic Changes in Chromatin Accessibility Occur in CD8+T Cells Responding to Viral Infection.
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.
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Scott-Browne
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA.
authors.forename: Isaac F
authors.initials: IF
authors.lastname: López-Moyado
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Trifari
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Lukas
authors.initials: L
authors.lastname: Chavez
authors.affiliation: 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.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute, 9420 Athena Circle, San Diego, CA 92037, USA.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Pereira
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002843:Chromatin; D042002:Chromatin Assembly and Disassembly / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology*; D020869:Gene Expression Profiling; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D002843:Chromatin