{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:44:56Z","timestamp":1792629896493,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b3 (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.<\/jats:p>","DOI":"10.4049\/jimmunol.1003741","type":"journal-article","created":{"date-parts":[[2011,1,29]],"date-time":"2011-01-29T02:21:21Z","timestamp":1296267681000},"page":"2705-2709","source":"Crossref","is-referenced-by-count":74,"title":["Cutting Edge: Persistently Open Chromatin at Effector Gene Loci in Resting Memory CD8+ T Cells Independent of Transcriptional Status"],"prefix":"10.1093","volume":"186","author":[{"given":"Valerie P","family":"Zediak","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B","family":"Johnnidis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Institute for Immunology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley L","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Department of Biology, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Department of Genetics, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,3,1]]},"reference":[{"key":"2025032411122041900_r1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.immuni.2007.08.007","article-title":"Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection","volume":"27","author":"Kaech","year":"2007","journal-title":"Immunity"},{"key":"2025032411122041900_r2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08830189509061734","article-title":"Cell-mediated cytotoxicity in perforin-less mice","volume":"13","author":"Clark","year":"1995","journal-title":"Int. Rev. Immunol."},{"key":"2025032411122041900_r3","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1006\/viro.1995.1477","article-title":"An essential role for type 1 interferon-gamma in terminating persistent viral infection","volume":"212","author":"Tishon","year":"1995","journal-title":"Virology"},{"key":"2025032411122041900_r4","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","article-title":"High-resolution profiling of histone methylations in the human genome","volume":"129","author":"Barski","year":"2007","journal-title":"Cell"},{"key":"2025032411122041900_r5","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cell.2008.02.022","article-title":"Dynamic regulation of nucleosome positioning in the human genome","volume":"132","author":"Schones","year":"2008","journal-title":"Cell"},{"key":"2025032411122041900_r6","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2006.02.041","article-title":"A bivalent chromatin structure marks key developmental genes in embryonic stem cells","volume":"125","author":"Bernstein","year":"2006","journal-title":"Cell"},{"key":"2025032411122041900_r7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cell.2007.05.042","article-title":"A chromatin landmark and transcription initiation at most promoters in human cells","volume":"130","author":"Guenther","year":"2007","journal-title":"Cell"},{"key":"2025032411122041900_r8","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.immuni.2010.04.016","article-title":"Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage","volume":"32","author":"Mukasa","year":"2010","journal-title":"Immunity"},{"key":"2025032411122041900_r9","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.immuni.2009.05.006","article-title":"Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T cells","volume":"30","author":"Araki","year":"2009","journal-title":"Immunity"},{"key":"2025032411122041900_r10","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1002\/eji.1830171226","article-title":"Molecular analysis of the antigen receptor of virus-specific cytotoxic T cells and identification of a new V alpha family","volume":"17","author":"Pircher","year":"1987","journal-title":"Eur. J. Immunol."},{"key":"2025032411122041900_r11","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.4049\/jimmunol.176.7.4083","article-title":"Rapid demethylation of the IFN-gamma gene occurs in memory but not naive CD8 T cells","volume":"176","author":"Kersh","year":"2006","journal-title":"J. Immunol."},{"key":"2025032411122041900_r12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.20081242","article-title":"Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs","volume":"206","author":"Cruz-Guilloty","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032411122041900_r13","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0092-8674(02)01139-X","article-title":"Molecular and functional profiling of memory CD8 T cell differentiation","volume":"111","author":"Kaech","year":"2002","journal-title":"Cell"},{"key":"2025032411122041900_r14","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"2025032411122041900_r15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.cell.2009.02.043","article-title":"Mechanisms that specify promoter nucleosome location and identity","volume":"137","author":"Hartley","year":"2009","journal-title":"Cell"},{"key":"2025032411122041900_r16","doi-asserted-by":"crossref","first-page":"7063","DOI":"10.4049\/jimmunol.0901522","article-title":"Interplay between chromatin remodeling and epigenetic changes during lineage-specific commitment to granzyme B expression. [Published erratum appears in 2010 J. Immunol. 184: 1653.]","volume":"183","author":"Juelich","year":"2009","journal-title":"J. Immunol."},{"key":"2025032411122041900_r17","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.4049\/jimmunol.175.7.4465","article-title":"Analyzing expression of perforin, Runx3, and Thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes","volume":"175","author":"Liu","year":"2005","journal-title":"J. Immunol."},{"key":"2025032411122041900_r18","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1084\/jem.181.2.755","article-title":"Transcription of granzyme A and B genes is differentially regulated during lymphoid ontogeny","volume":"181","author":"Ebnet","year":"1995","journal-title":"J. Exp. Med."},{"key":"2025032411122041900_r19","doi-asserted-by":"crossref","first-page":"8102","DOI":"10.4049\/jimmunol.180.12.8102","article-title":"Histone acetylation facilitates rapid and robust memory CD8 T cell response through differential expression of effector molecules (eomesodermin and its targets: perforin and granzyme B)","volume":"180","author":"Araki","year":"2008","journal-title":"J. Immunol."},{"key":"2025032411122041900_r20","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1182\/blood-2006-02-005520","article-title":"Histone acetylation is associated with differential gene expression in the rapid and robust memory CD8(+) T-cell response","volume":"108","author":"Fann","year":"2006","journal-title":"Blood"},{"key":"2025032411122041900_r21","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.immuni.2010.06.014","article-title":"Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation","volume":"33","author":"Wirth","year":"2010","journal-title":"Immunity"},{"key":"2025032411122041900_r22","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.cell.2007.08.016","article-title":"Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4","volume":"131","author":"Vermeulen","year":"2007","journal-title":"Cell"},{"key":"2025032411122041900_r23","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.immuni.2008.12.009","article-title":"Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells","volume":"30","author":"Wei","year":"2009","journal-title":"Immunity"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/5\/2705\/62476475\/1003741.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/5\/2705\/62476475\/1003741.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T11:29:09Z","timestamp":1743161349000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/186\/5\/2705\/7990271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,1]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1003741","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,3]]},"published":{"date-parts":[[2011,3,1]]}}}