title: Cutting edge: persistently open chromatin at effector gene loci in resting memory CD8+ T cells independent of transcriptional status.
abstract: Memory CD8(+) T cells are characterized by more rapid and robust effector function upon infection compared with naive T cells, but factors governing effector gene responsiveness are incompletely understood. We sought to understand transcriptional control of the effector genes IFN-γ (Ifng), granzyme B (Gzmb), and perforin 1 (Prf1) in murine memory CD8(+) T cells by characterizing their transcriptional profiles and chromatin states during lymphocytic choriomeningitis virus infection. Each effector gene has a distinct transcriptional profile in resting memory cells and following restimulation. Primary infection leads to reduced nucleosomal density near the transcription start sites and reduced H3K27 methylation throughout the Ifng and Gzmb loci, and these chromatin changes persist in the memory phase. Despite similarities in chromatin at the memory stage, PolII recruitment and continuous transcription occur at the Ifng locus but not the Gzmb locus. We propose that these chromatin changes poise effector genes for rapid upregulation, but are insufficient for PolII recruitment and transcription.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Valerie P
authors.initials: VP
authors.lastname: Zediak
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Johnnidis
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020869:Gene Expression Profiling; D056426:Genetic Loci / Q000276:immunology*; D053804:Granzymes / Q000096:biosynthesis / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000276:immunology*
chemical_list: D002843:Chromatin; D052899:Pore Forming Cytotoxic Proteins; C510467:perforin 1, mouse; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes