Product(s) used in this publication: Single Kinase Substrate Peptides
MemoryTcells are characterized by their rapidtranscriptional programs upon re-stimulation. This transcriptionalmemory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memoryTcells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo humanCD4(+) Tcells, 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 humanmemoryCD4(+) Tcells. 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 transcriptionalmemory 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 transcriptionalmemoryresponses in humanmemoryTcells.