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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.

Original publication

DOI

10.1242/jcs.181248

Type

Journal article

Journal

J Cell Sci

Publication Date

15/06/2016

Volume

129

Pages

2448 - 2461

Keywords

Chromatin, Memory, PKC-θ, T-cells, Transcription, Amino Acid Sequence, CD4-Positive T-Lymphocytes, Cell Nucleus, Chromatin, Gene Expression Regulation, Histones, Humans, Immunologic Memory, Isoenzymes, Jurkat Cells, Phosphorylation, Phosphoserine, Protein Kinase C, Protein Kinase C-theta, Signal Transduction, Transcription Factor RelA, Transcription, Genetic