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Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8 T cell differentiation


Russ, BE; Olshanksy, M; Smallwood, HS; Li, J; Denton, AE; Prier, JE; Stock, AT; Croom, HA; Cullen, JG; Nguyen, ML; Rowe, S; Olson, MR; Finkelstein, DB; Kelso, A; Thomas, PG; Speed, TP; Rao, S; Turner, SJ
2014-11-20
Immunity
Journal Article
41
5
853-865
The molecular mechanisms that regulate the rapid transcriptional changes that occur during cytotoxic T lymphocyte (CTL) proliferation and differentiation in response to infection are poorly understood. We have utilized ChIP-seq to assess histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection. Our results show that within naive T cells, codeposition of the permissive H3K4me3 and repressive H3K27me3 modifications is a signature of gene loci associated with gene transcription, replication, and cellular differentiation. Upon differentiation into effector and/or memory CTLs, the majority of these gene loci lose repressive H3K27me3 while retaining the permissive H3K4me3 modification. In contrast, immune-related effector gene promoters within naive T cells lacked the permissive H3K4me3 modification, with acquisition of this modification occurring upon differentiation into effector/memory CTLs. Thus, coordinate transcriptional regulation of CTL genes with related functions is achieved via distinct epigenetic mechanisms.
Cell Press
Bioinformatics
10.1016/j.immuni.2014.11.001
Copyright © 2014 Elsevier Inc. All rights reserved.

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Creation Date 2014-12-19 11:44:54 Last Modified 2016-04-20 10:25:28