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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Company of Biologists Ltd
2016
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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. |
format | Online Article Text |
id | pubmed-4920249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
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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