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

Autor:	Russ BE; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Olshanksy M; Department of Bioinformatics, Walter and Eliza Hall Institute, Parkville, VIC 3010, Australia., Smallwood HS; Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Li J; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Denton AE; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Prier JE; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Stock AT; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Croom HA; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Cullen JG; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Nguyen ML; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Rowe S; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Olson MR; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia., Finkelstein DB; Hartwell Centre for Bioinformatics and Biotechnology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Kelso A; 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., Thomas PG; Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Speed TP; Department of Bioinformatics, Walter and Eliza Hall Institute, Parkville, VIC 3010, Australia., Rao S; Department of Molecular and Cellular Biology, Canberra University, Canberra, ACT 2000, Australia., Turner SJ; Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: sjturn@unimelb.edu.au.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2014 Nov 20; Vol. 41 (5), pp. 853-65. Date of Electronic Publication: 2014 Nov 06.
DOI:	10.1016/j.immuni.2014.11.001
Abstrakt:	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. (Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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