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

Brendan Russ, Moshe Olshanksy, Heather Smallwood, Jasmine Li, Alice Denton, Julia Prier, Angus Stock, Hayley Croom, Jolie Cullen, Michelle Nguyen, Stephanie Rowe, Matthew Olson, David Finkelstein, Anne Kelso, Paul Thomas, Terence Speed, Sudha RAO, Stephen J. Turner

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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 - 2014

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Russ, B., Olshanksy, M., Smallwood, H., Li, J., Denton, A., Prier, J., ... Turner, S. J. (2014). Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8+ T cell differentiation. Immunity, 41(5), 853-865. https://doi.org/10.1016/j.immuni.2014.11.001