Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory
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...
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Published in | The Journal of immunology (1950) Vol. 198; no. 6; pp. 2238 - 2243 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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United States
American Association of Immunologists
15.03.2017
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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
-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
-element usage, thereby reducing the steps necessary to revive effector functions. |
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AbstractList | 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. 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. 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 -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 -element usage, thereby reducing the steps necessary to revive effector functions. |
Author | Bally, Alexander P R Boss, Jeremy M Gandham, Bhanu Scharer, Christopher D |
Author_xml | – sequence: 1 givenname: Christopher D orcidid: 0000-0001-7716-8504 surname: Scharer fullname: Scharer, Christopher D organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 – sequence: 2 givenname: Alexander P R orcidid: 0000-0003-4494-5033 surname: Bally fullname: Bally, Alexander P R organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 – sequence: 3 givenname: Bhanu orcidid: 0000-0002-4027-1062 surname: Gandham fullname: Gandham, Bhanu organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 – sequence: 4 givenname: Jeremy M orcidid: 0000-0002-2432-1840 surname: Boss fullname: Boss, Jeremy M email: jmboss@emory.edu organization: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 jmboss@emory.edu |
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Snippet | CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive... Abstract CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the... |
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SubjectTerms | Animals Arenaviridae CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - virology Cell Proliferation Cells, Cultured Chromatin Chromatin - immunology Chromatin Assembly and Disassembly Gene expression Genes Immunologic Memory - genetics Immunological memory Lymphocyte Activation Lymphocytes Lymphocytes T Lymphocytic Choriomeningitis - immunology Lymphocytic choriomeningitis virus - immunology Memory cells Mice Mice, Inbred C57BL Molecular modelling Regulatory sequences Sequence Analysis, DNA T cell receptors T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - virology Transposase Transposases - metabolism Viruses |
Title | Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory |
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