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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Company of Biologists
2018
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| _version_ | 1797051752770437120 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Li, J |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-06T18:23:58Z |
| format | Journal article |
| id | oxford-uuid:074a0cf3-c95b-4ef5-ab83-8e06b51a4b6e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:23:58Z |
| publishDate | 2018 |
| publisher | Company of Biologists |
| record_format | dspace |
| spelling | oxford-uuid:074a0cf3-c95b-4ef5-ab83-8e06b51a4b6e2022-03-26T09:06:50ZNuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:074a0cf3-c95b-4ef5-ab83-8e06b51a4b6eEnglishSymplectic Elements at OxfordCompany of Biologists2018Li, JHardy, KPhetsouphanh, CTu, WJSutcliffe, ELMcCuaig, RSutton, CRZafar, AMunier, CMLZaunders, JJXu, YTheodoratos, ATan, ALim, PSKnaute, TMasch, AZerweck, JBrezar, VMilburn, PJDunn, JCasarotto, MGTurner, SJSeddiki, NKelleher, ADRao, SMemory 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. |
| spellingShingle | 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 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 |
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