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

Brendan E. Russ, Moshe Olshanksy, Heather S. Smallwood, Jasmine Li, Alice E Denton, Julia E Prier, Angus T. Stock, Hayley A Croom, Jolie G. Cullen, Michelle L.T. Nguyen, Stephanie Rowe, Matthew R. Olson, David B. Finkelstein, Anne Kelso, Paul G. Thomas, Terry P. Speed, Sudha Rao, Stephen J. Turner

Research output: Contribution to journalArticleResearchpeer-review

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 - 20 Nov 2014
Externally publishedYes

Cite this

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. / 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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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 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.",
author = "Russ, {Brendan E.} and Moshe Olshanksy and Smallwood, {Heather S.} and Jasmine Li and Denton, {Alice E} and Prier, {Julia E} and Stock, {Angus T.} and Croom, {Hayley A} and Cullen, {Jolie G.} and Nguyen, {Michelle L.T.} and Stephanie Rowe and Olson, {Matthew R.} and Finkelstein, {David B.} and Anne Kelso and Thomas, {Paul G.} and Speed, {Terry P.} and Sudha Rao and Turner, {Stephen J.}",
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Russ, BE, Olshanksy, M, Smallwood, HS, Li, J, Denton, AE, Prier, JE, Stock, AT, Croom, HA, Cullen, JG, Nguyen, MLT, Rowe, S, Olson, MR, Finkelstein, DB, Kelso, A, Thomas, PG, Speed, TP, 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 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.

In: Immunity, Vol. 41, No. 5, 20.11.2014, p. 853-865.

Research output: Contribution to journalArticleResearchpeer-review

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

AU - Russ, Brendan E.

AU - Olshanksy, Moshe

AU - Smallwood, Heather S.

AU - Li, Jasmine

AU - Denton, Alice E

AU - Prier, Julia E

AU - Stock, Angus T.

AU - Croom, Hayley A

AU - Cullen, Jolie G.

AU - Nguyen, Michelle L.T.

AU - Rowe, Stephanie

AU - Olson, Matthew R.

AU - Finkelstein, David B.

AU - Kelso, Anne

AU - Thomas, Paul G.

AU - Speed, Terry P.

AU - Rao, Sudha

AU - Turner, Stephen J.

PY - 2014/11/20

Y1 - 2014/11/20

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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DO - 10.1016/j.immuni.2014.11.001

M3 - Article

VL - 41

SP - 853

EP - 865

JO - Immunity

JF - Immunity

SN - 1074-7613

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