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

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 unde...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920249/
https://www.ncbi.nlm.nih.gov/pubmed/27149922
http://dx.doi.org/10.1242/jcs.181248
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author 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
author_facet 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
author_sort Li, Jasmine
collection PubMed
description 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.
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spelling pubmed-49202492016-07-14 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 J Cell Sci Research Article 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. The Company of Biologists Ltd 2016-06-15 /pmc/articles/PMC4920249/ /pubmed/27149922 http://dx.doi.org/10.1242/jcs.181248 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
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
title Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4(+) T cells through p65 and H2B phosphorylation
title_full Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4(+) T cells through p65 and H2B phosphorylation
title_fullStr Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4(+) T cells through p65 and H2B phosphorylation
title_full_unstemmed Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4(+) T cells through p65 and H2B phosphorylation
title_short Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4(+) T cells through p65 and H2B phosphorylation
title_sort nuclear pkc-θ facilitates rapid transcriptional responses in human memory cd4(+) t cells through p65 and h2b phosphorylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920249/
https://www.ncbi.nlm.nih.gov/pubmed/27149922
http://dx.doi.org/10.1242/jcs.181248
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