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

Research output: Contribution to journalArticle

79 Citations (Scopus)

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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Epigenomics
Cell Differentiation
Viruses
T-Lymphocytes
Genes
Cytotoxic T-Lymphocytes
Influenza A virus
Virus Diseases
Histones
Methylation
Infection

Cite this

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
Russ, Brendan ; Olshanksy, Moshe ; Smallwood, Heather ; Li, Jasmine ; Denton, Alice ; Prier, Julia ; Stock, Angus ; Croom, Hayley ; Cullen, Jolie ; Nguyen, Michelle ; Rowe, Stephanie ; Olson, Matthew ; Finkelstein, David ; Kelso, Anne ; Thomas, Paul ; Speed, Terence ; RAO, Sudha ; Turner, Stephen J. / Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8+ T cell differentiation. In: Immunity. 2014 ; Vol. 41, No. 5. pp. 853-865.
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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.",
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Russ, B, Olshanksy, M, Smallwood, H, Li, J, Denton, A, Prier, J, Stock, A, Croom, H, Cullen, J, Nguyen, M, Rowe, S, Olson, M, Finkelstein, D, Kelso, A, Thomas, P, Speed, T, RAO, S & Turner, SJ 2014, 'Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8+ T cell differentiation', Immunity, vol. 41, no. 5, pp. 853-865. https://doi.org/10.1016/j.immuni.2014.11.001

Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8+ T cell differentiation. / Russ, Brendan; Olshanksy, Moshe; Smallwood, Heather; Li, Jasmine; Denton, Alice; Prier, Julia; Stock, Angus; Croom, Hayley; Cullen, Jolie; Nguyen, Michelle; Rowe, Stephanie; Olson, Matthew; Finkelstein, David; Kelso, Anne; Thomas, Paul; Speed, Terence; RAO, Sudha; Turner, Stephen J.

In: Immunity, Vol. 41, No. 5, 2014, p. 853-865.

Research output: Contribution to journalArticle

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T1 - Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8+ T cell differentiation

AU - Russ, Brendan

AU - Olshanksy, Moshe

AU - Smallwood, Heather

AU - Li, Jasmine

AU - Denton, Alice

AU - Prier, Julia

AU - Stock, Angus

AU - Croom, Hayley

AU - Cullen, Jolie

AU - Nguyen, Michelle

AU - Rowe, Stephanie

AU - Olson, Matthew

AU - Finkelstein, David

AU - Kelso, Anne

AU - Thomas, Paul

AU - Speed, Terence

AU - RAO, Sudha

AU - Turner, Stephen J.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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KW - Epigenesis, Genetic/immunology

KW - Histones/genetics

KW - Immunologic Memory

KW - Influenza A virus/immunology

KW - Lymphocyte Activation/immunology

KW - Mice

KW - Mice, Inbred C57BL

KW - Orthomyxoviridae Infections/immunology

KW - Protein Processing, Post-Translational

KW - T-Lymphocytes, Cytotoxic/cytology

KW - Transcription, Genetic/immunology

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DO - 10.1016/j.immuni.2014.11.001

M3 - Article

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