Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 12, Pages 2448-2461Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.181248
Keywords
Chromatin; Memory; PKC-theta; T-cells; Transcription
Categories
Funding
- National Health and Medical Research Council (Australia) [APP1025718]
Ask authors/readers for more resources
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-theta) 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-kappa B motifs in ex vivo bulk and vaccinia-responsive human memory CD4(+) T cells. Within the nucleus, PKC-theta catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-kappa B (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-theta mutant, we highlight that chromatin-anchored PKC-theta integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available