Mapping histone methylation dynamics during virus-specific CD8+ T cell differentiation in response to infection

• Published in: Immunity (Cambridge, Mass.) Mass.), 2014-11, Vol.41 (5), p.853-865
• Main Authors: Russ, Brendan E., Olshanksy, Moshe, Smallwood, Heather S., Li, Jasmine, Denton, Alice E., Prier, Julia E., Stock, Angus T., Croom, Hayley A., Cullen, Jolie G., Nguyen, Michelle L. T., Rowe, Stephanie, Olson, Matthew R., Finkelstein, David B., Kelso, Anne, Thomas, Paul G., Speed, Terry P., Rao, Sudha, Turner, Stephen J.
• Format: Article
• Language: English
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2014.11.001

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 utilised ChIP-seq to assess histone H3 methylation dynamics within naïve, effector and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection. Our results show that within naïve T cells, co-deposition 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 CTL, the majority of these gene loci lose the repressive H3K27me3 while retaining the permissive H3K4me3 modification. In contrast, immune-related effector gene promoters within naïve T cells lacked the permissive H3K4me3 modification, with acquisition of this modification occurring upon differentiation into effector/memory CTL. Thus, coordinate transcriptional regulation of CTL genes with related functions is achieved using distinct epigenetic mechanisms.