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, Cynthia Mee Ling Munier, John Zaunders, Yin Xu, Angelo Theodoratos, Abel Tan, Pek SiewLim, Tobias Knaute, Antonia Masch, Johannes Zerweck, Vedran Brezar, Peter J. Milburn, Jenny DunnMarco G Casarotto, Stephen J. Turner, Nabila Seddiki, Anthony D Kelleher, Sudha Rao

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11 Citations (Scopus)


MemoryTcells are characterizedby 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-wideChIP-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
Issue number12
Publication statusPublished - 15 Jun 2016
Externally publishedYes


  • Chromatin
  • Memory
  • PKC-θ
  • T-cells
  • Transcription

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