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

Brendan E. Russ, Moshe Olshanksy, Heather S. Smallwood, Jasmine Li, Alice E Denton, Julia E Prier, Angus T. Stock, Hayley A Croom, Jolie G. Cullen, Michelle L.T. Nguyen, Stephanie Rowe, Matthew R. Olson, David B. Finkelstein, Anne Kelso, Paul G. Thomas, Terry P. Speed, Sudha Rao, Stephen J. Turner

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83 Citations (Scopus)

Abstract

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 Tcells isolated directly exvivo after influenza A virus infection. Our results show that within naive Tcells, 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 Tcells 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.

Original languageEnglish
Pages (from-to)853-865
Number of pages13
JournalImmunity
Volume41
Issue number5
DOIs
Publication statusPublished - 20 Nov 2014
Externally publishedYes

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