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Immunity. 2014 Nov 20;41(5):853-65. doi: 10.1016/j.immuni.2014.11.001. Epub 2014 Nov 6.

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

Author information

1
Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
2
Department of Bioinformatics, Walter and Eliza Hall Institute, Parkville, VIC 3010, Australia.
3
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Hartwell Centre for Bioinformatics and Biotechnology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
5
Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia; WHO Collaborating Centre for Reference and Research on Influenza, The Doherty Institute at the University of Melbourne, Parkville, VIC 3010, Australia.
6
Department of Molecular and Cellular Biology, Canberra University, Canberra, ACT 2000, Australia.
7
Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: sjturn@unimelb.edu.au.

Erratum in

  • Immunity. 2014 Dec 18;41(6):1064.

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 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.

PMID:
25517617
PMCID:
PMC4479393
DOI:
10.1016/j.immuni.2014.11.001
[Indexed for MEDLINE]
Free PMC Article

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