Cutting edge: chromatin accessibility programs CD8 T cell memory

CD Scharer, APR Bally, B Gandham… - The Journal of …, 2017 - journals.aai.org
CD Scharer, APR Bally, B Gandham, JM Boss
The Journal of Immunology, 2017journals.aai.org
CD8 T cell memory is characterized by rapid recall of effector function, increased
proliferation, and reduced activation requirements. Despite the extensive functional
characterization, the molecular mechanisms that facilitate these enhanced properties are not
well characterized. In this study, the assay for transposase-accessible chromatin sequencing
was employed to map the cis-regulatory elements in CD8 T cells responding to acute and
chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility …
Abstract
CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor–binding motifs. Memory CD8 T cells displayed a chromatin accessibility structure that was absent from other acute and exhausted cells types and included key effector and proliferative genes. Stimulation of memory cells revealed enhanced transcription of “memory-primed” genes compared with naive cells. Thus, memory CD8 T cells display a preprogrammed chromatin accessibility profile and maintain a molecular history of cis-element usage, thereby reducing the steps necessary to revive effector functions.
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