Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function

Brendan E. Russ, Moshe Olshansky, Jasmine Li, Michelle L.T. Nguyen, Linden J. Gearing, Thi H.O. Nguyen, Matthew R. Olson, Hayley A. McQuilton, Simone Nüssing, Georges Khoury, Damian F.J. Purcell, Paul J. Hertzog, Sudha Rao, Stephen J. Turner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs), we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs) differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+) chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation. Russ et al. demonstrate that a subset of poised transcriptional enhancers found in naive virus-specific CD8+ T cells acquire a non-canonical chromatin signature upon differentiation. These data provide the genomic location for T cell lineage-specific transcription factor binding that is necessary for virus-specific T cell differentiation.

Original languageEnglish
Pages (from-to)3624-3636
Number of pages13
JournalCell Reports
Volume21
Issue number12
DOIs
Publication statusPublished - 19 Dec 2017

Keywords

  • CD8+ T cell
  • chromatin
  • epigenetics
  • influenza
  • transcription factor

Cite this

Russ, Brendan E. ; Olshansky, Moshe ; Li, Jasmine ; Nguyen, Michelle L.T. ; Gearing, Linden J. ; Nguyen, Thi H.O. ; Olson, Matthew R. ; McQuilton, Hayley A. ; Nüssing, Simone ; Khoury, Georges ; Purcell, Damian F.J. ; Hertzog, Paul J. ; Rao, Sudha ; Turner, Stephen J. / Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function. In: Cell Reports. 2017 ; Vol. 21, No. 12. pp. 3624-3636.
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title = "Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function",
abstract = "Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs), we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs) differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+) chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation. Russ et al. demonstrate that a subset of poised transcriptional enhancers found in naive virus-specific CD8+ T cells acquire a non-canonical chromatin signature upon differentiation. These data provide the genomic location for T cell lineage-specific transcription factor binding that is necessary for virus-specific T cell differentiation.",
keywords = "CD8+ T cell, chromatin, epigenetics, influenza, transcription factor",
author = "Russ, {Brendan E.} and Moshe Olshansky and Jasmine Li and Nguyen, {Michelle L.T.} and Gearing, {Linden J.} and Nguyen, {Thi H.O.} and Olson, {Matthew R.} and McQuilton, {Hayley A.} and Simone N{\"u}ssing and Georges Khoury and Purcell, {Damian F.J.} and Hertzog, {Paul J.} and Sudha Rao and Turner, {Stephen J.}",
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Russ, BE, Olshansky, M, Li, J, Nguyen, MLT, Gearing, LJ, Nguyen, THO, Olson, MR, McQuilton, HA, Nüssing, S, Khoury, G, Purcell, DFJ, Hertzog, PJ, Rao, S & Turner, SJ 2017, 'Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function', Cell Reports, vol. 21, no. 12, pp. 3624-3636. https://doi.org/10.1016/j.celrep.2017.11.097

Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function. / Russ, Brendan E.; Olshansky, Moshe; Li, Jasmine; Nguyen, Michelle L.T.; Gearing, Linden J.; Nguyen, Thi H.O.; Olson, Matthew R.; McQuilton, Hayley A.; Nüssing, Simone; Khoury, Georges; Purcell, Damian F.J.; Hertzog, Paul J.; Rao, Sudha; Turner, Stephen J.

In: Cell Reports, Vol. 21, No. 12, 19.12.2017, p. 3624-3636.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Russ, Brendan E.

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AU - Nguyen, Michelle L.T.

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AU - Olson, Matthew R.

AU - McQuilton, Hayley A.

AU - Nüssing, Simone

AU - Khoury, Georges

AU - Purcell, Damian F.J.

AU - Hertzog, Paul J.

AU - Rao, Sudha

AU - Turner, Stephen J.

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AB - Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs), we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs) differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+) chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation. Russ et al. demonstrate that a subset of poised transcriptional enhancers found in naive virus-specific CD8+ T cells acquire a non-canonical chromatin signature upon differentiation. These data provide the genomic location for T cell lineage-specific transcription factor binding that is necessary for virus-specific T cell differentiation.

KW - CD8+ T cell

KW - chromatin

KW - epigenetics

KW - influenza

KW - transcription factor

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