Li, JasmineHardy, KristinePhetsouphanh, ChanTu, Wen JuanSutcliffe, Elissa LMcCuaig, RobertSutton, Christopher RZafar, AnjumMunier, C Mee LingZaunders, John JXu, YinTheodoratos, AngeloTan, AbelLim, Pek SiewKnaute, TobiasMasch, AntoniaZerweck, JohannesBrezar, VedranMilburn, Peter JDunn, JennyCasarotto, Marco GTurner, Stephen JSeddiki, NabilaKelleher, Anthony DRao, Sudha2017-02-212017-02-210021-9533http://hdl.handle.net/1885/112477Memory 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.This work was supported by the National Health and Medical Research Council (Australia) [grant number APP1025718 to S.R. and N.S.].24 pagesapplication/pdfThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.chromatinmemorypkc-θt-cellstranscription2016-06-1510.1242/jcs.181248