Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation

Jasmine Li, Kristine Hardy, Chan Phetsouphanh, Wen Juan Tu, Elissa L Sutcliffe, Robert McCuaig, Christopher R Sutton, Anjum Zafar, C Mee Ling Munier, John J Zaunders, Yin Xu, Angelo Theodoratos, Abel Tan, Pek Siew Lim, Tobias Knaute, Antonia Masch, Johannes Zerweck, Vedran Brezar, Peter J Milburn, Jenny Dunn & 5 others Marco G Casarotto, Stephen J Turner, Nabila Seddiki, Anthony D Kelleher, Sudha Rao

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4(+) T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells.

Original languageEnglish
Pages (from-to)2448-2461
Number of pages14
JournalJournal of Cell Science
Volume129
Issue number12
DOIs
Publication statusPublished - 2016

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Nuclear Proteins
Protein Kinase C
Chromatin
Phosphorylation
T-Lymphocytes
Histone Code
Vaccinia
Epigenomics
Transcriptional Activation
Genes
Cytoplasm
Genome
Enzymes

Cite this

Li, J., Hardy, K., Phetsouphanh, C., Tu, W. J., Sutcliffe, E. L., McCuaig, R., ... Rao, S. (2016). Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation. Journal of Cell Science, 129(12), 2448-2461. https://doi.org/10.1242/jcs.181248
Li, Jasmine ; Hardy, Kristine ; Phetsouphanh, Chan ; Tu, Wen Juan ; Sutcliffe, Elissa L ; McCuaig, Robert ; Sutton, Christopher R ; Zafar, Anjum ; Munier, C Mee Ling ; Zaunders, John J ; Xu, Yin ; Theodoratos, Angelo ; Tan, Abel ; Lim, Pek Siew ; Knaute, Tobias ; Masch, Antonia ; Zerweck, Johannes ; Brezar, Vedran ; Milburn, Peter J ; Dunn, Jenny ; Casarotto, Marco G ; Turner, Stephen J ; Seddiki, Nabila ; Kelleher, Anthony D ; Rao, Sudha. / Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation. In: Journal of Cell Science. 2016 ; Vol. 129, No. 12. pp. 2448-2461.
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title = "Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation",
abstract = "Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4(+) T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells.",
keywords = "Amino Acid Sequence, CD4-Positive T-Lymphocytes/metabolism, Cell Nucleus/enzymology, Chromatin/metabolism, Gene Expression Regulation, Histones/chemistry, Humans, Immunologic Memory/genetics, Isoenzymes/metabolism, Jurkat Cells, Phosphorylation, Phosphoserine/metabolism, Protein Kinase C/metabolism, Protein Kinase C-theta, Signal Transduction, Transcription Factor RelA/metabolism, Transcription, Genetic",
author = "Jasmine Li and Kristine Hardy and Chan Phetsouphanh and Tu, {Wen Juan} and Sutcliffe, {Elissa L} and Robert McCuaig and Sutton, {Christopher R} and Anjum Zafar and Munier, {C Mee Ling} and Zaunders, {John J} and Yin Xu and Angelo Theodoratos and Abel Tan and Lim, {Pek Siew} and Tobias Knaute and Antonia Masch and Johannes Zerweck and Vedran Brezar and Milburn, {Peter J} and Jenny Dunn and Casarotto, {Marco G} and Turner, {Stephen J} and Nabila Seddiki and Kelleher, {Anthony D} and Sudha Rao",
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Li, J, Hardy, K, Phetsouphanh, C, Tu, WJ, Sutcliffe, EL, McCuaig, R, Sutton, CR, Zafar, A, Munier, CML, Zaunders, JJ, Xu, Y, Theodoratos, A, Tan, A, Lim, PS, Knaute, T, Masch, A, Zerweck, J, Brezar, V, Milburn, PJ, Dunn, J, Casarotto, MG, Turner, SJ, Seddiki, N, Kelleher, AD & Rao, S 2016, 'Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation', Journal of Cell Science, vol. 129, no. 12, pp. 2448-2461. https://doi.org/10.1242/jcs.181248

Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation. / Li, Jasmine; Hardy, Kristine; Phetsouphanh, Chan; Tu, Wen Juan; Sutcliffe, Elissa L; McCuaig, Robert; Sutton, Christopher R; Zafar, Anjum; Munier, C Mee Ling; Zaunders, John J; Xu, Yin; Theodoratos, Angelo; Tan, Abel; Lim, Pek Siew; Knaute, Tobias; Masch, Antonia; Zerweck, Johannes; Brezar, Vedran; Milburn, Peter J; Dunn, Jenny; Casarotto, Marco G; Turner, Stephen J; Seddiki, Nabila; Kelleher, Anthony D; Rao, Sudha.

In: Journal of Cell Science, Vol. 129, No. 12, 2016, p. 2448-2461.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation

AU - Li, Jasmine

AU - Hardy, Kristine

AU - Phetsouphanh, Chan

AU - Tu, Wen Juan

AU - Sutcliffe, Elissa L

AU - McCuaig, Robert

AU - Sutton, Christopher R

AU - Zafar, Anjum

AU - Munier, C Mee Ling

AU - Zaunders, John J

AU - Xu, Yin

AU - Theodoratos, Angelo

AU - Tan, Abel

AU - Lim, Pek Siew

AU - Knaute, Tobias

AU - Masch, Antonia

AU - Zerweck, Johannes

AU - Brezar, Vedran

AU - Milburn, Peter J

AU - Dunn, Jenny

AU - Casarotto, Marco G

AU - Turner, Stephen J

AU - Seddiki, Nabila

AU - Kelleher, Anthony D

AU - Rao, Sudha

N1 - © 2016. Published by The Company of Biologists Ltd.

PY - 2016

Y1 - 2016

N2 - Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4(+) T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells.

AB - Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4(+) T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells.

KW - Amino Acid Sequence

KW - CD4-Positive T-Lymphocytes/metabolism

KW - Cell Nucleus/enzymology

KW - Chromatin/metabolism

KW - Gene Expression Regulation

KW - Histones/chemistry

KW - Humans

KW - Immunologic Memory/genetics

KW - Isoenzymes/metabolism

KW - Jurkat Cells

KW - Phosphorylation

KW - Phosphoserine/metabolism

KW - Protein Kinase C/metabolism

KW - Protein Kinase C-theta

KW - Signal Transduction

KW - Transcription Factor RelA/metabolism

KW - Transcription, Genetic

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UR - http://www.mendeley.com/research/nuclear-pkc%CE%B8-facilitates-rapid-transcriptional-responses-human-memory-cd4-t-cells-through-p65-h2b-ph

U2 - 10.1242/jcs.181248

DO - 10.1242/jcs.181248

M3 - Article

VL - 129

SP - 2448

EP - 2461

JO - The Quarterly journal of microscopical science

JF - The Quarterly journal of microscopical science

SN - 0021-9533

IS - 12

ER -