Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation
| Autor: | Elissa L Sutcliffe, John Zaunders, C Mee Ling Munier, Jasmine Li, Peter J. Milburn, Abel Tan, Angelo Theodoratos, Anthony D. Kelleher, Pek Siew Lim, Stephen J. Turner, Nabila Seddiki, Sudha Rao, Chan Phetsouphanh, Vedran Brezar, Tobias Knaute, Kristine Hardy, Anjum Zafar, Marco G. Casarotto, Antonia Masch, Christopher R Sutton, Wen Juan Tu, Jenny Dunn, Robert McCuaig, Johannes Zerweck, Yin Xu |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Transcription Genetic Jurkat cells Histones 03 medical and health sciences Jurkat Cells Phosphoserine 0302 clinical medicine PKC-θ Memory Humans Epigenetics Amino Acid Sequence Phosphorylation Protein kinase C Protein Kinase C Regulation of gene expression Cell Nucleus biology T-cells Transcription Factor RelA Cell Biology Molecular biology Chromatin Cell biology Isoenzymes 030104 developmental biology Histone Gene Expression Regulation Protein Kinase C-theta biology.protein Signal transduction Immunologic Memory Transcription 030215 immunology Signal Transduction Research Article |
| Zdroj: | Journal of Cell Science |
| Popis: | 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. Summary: Memory T cells have a rapid transcriptional program upon re-stimulation. Chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit this transcriptional memory in T cells. |
| Databáze: | OpenAIRE |
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