Dynamic changes in chromatin accessibility in CD8+ T cells responding to viral infection
| Autor: | Anjana Rao, Isaac F. López-Moyado, Victor Wong, Sara Trifari, Lukas Chavez, Renata M. Pereira, James P. Scott-Browne |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Immunology Gene Expression Mice Transgenic Biology CD8-Positive T-Lymphocytes Lymphocyte Activation Article 03 medical and health sciences Mice BATF Immunology and Allergy Cytotoxic T cell Animals Arenaviridae Infections Lymphocytic choriomeningitis virus Transcription factor Effector Gene Expression Profiling NFAT Chromatin Assembly and Disassembly Chromatin Mice Inbred C57BL Disease Models Animal 030104 developmental biology Infectious Diseases Immunologic Memory CD8 IRF4 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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