title: Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8(+) T cell differentiation.
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.
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Brendan E
authors.initials: BE
authors.lastname: Russ
authors.affiliation: Department of Bioinformatics, Walter and Eliza Hall Institute, Parkville, VIC 3010, Australia.
authors.forename: Moshe
authors.initials: M
authors.lastname: Olshanksy
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Smallwood
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Alice E
authors.initials: AE
authors.lastname: Denton
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Prier
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Angus T
authors.initials: AT
authors.lastname: Stock
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Hayley A
authors.initials: HA
authors.lastname: Croom
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Jolie G
authors.initials: JG
authors.lastname: Cullen
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Michelle L T
authors.initials: ML
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rowe
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Olson
authors.affiliation: Hartwell Centre for Bioinformatics and Biotechnology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Finkelstein
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Department of Bioinformatics, Walter and Eliza Hall Institute, Parkville, VIC 3010, Australia.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Speed
authors.affiliation: Department of Molecular and Cellular Biology, Canberra University, Canberra, ACT 2000, Australia.
authors.forename: Sudha
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Microbiology and Immunology, The Doherty Institute at The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: sjturn@unimelb.edu.au.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000276:immunology*; D006657:Histones / Q000235:genetics*; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011499:Protein Processing, Post-Translational; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D006657:Histones