Genome-wide mapping of p300 binding in resting and activated human naïve and memory CD8 T cells

ABSTRACT: Memory T cells (TM) play a prominent role in protective and auto-immunity because they mount a more effective response than naïve T cells (TN), by rapidly expressing a large number of immune response genes upon stimulation. Previous studies have shown a correlation between increased histone acetylation levels and rapid gene expression at specific loci in CD8+ TM. However, the underlying mechanisms of histone acetylation remodeling in TM and its role in regulating global gene expression are not well defined, particularly in human TM cells. In this study, we examined the global level of histone acetylation and the expression of histone acetyltransferases and deacetylases , and found no differences between human CD8+ TN and TM cells. Through Genomegenome-wide mapping of the histone acetyltransferase p300 in human CD8+ TN and TM cells, recruitment of p300 was found to be positively correlated with the expression of 213 genes in TM and 516 genes in TN cells at rest, and was positively correlated with the expression of 556 genes in TM and 330 genes in TN cells after 4 hrs’ stimulation. Importantly, genes which have positive correlations between expression levels and p300 occupancy in TM were significantly enriched in effector functions of CD8+ T cells, while those in TN cells were over-presented in nucleic acid processing and cell differentiations. At IFNG locus, specifically, the recruitment of p300 was significantly higher in CD8+ TM than TN and cells that were correlated with increased levels of histone acetylation at this locus, and robust IFN-g expression by CD8+ TM cells. Selective inhibition of p300 and deletion of p300 binding sites within the IFNG promoter resulted in decreased histone acetylation at this locus and the lower expression level of IFN-g in CD8+ TM cells. These results suggest that recruitment of the histone acetyltransferase p300 modifies histone acetylation and allows rapid expression of IFNG, and likely a large set of immune response genes, in human CD8+ TM, which in turn contribute to the enhanced functionality of human CD8+ TM cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93163 | GEO | 2017/01/05

SECONDARY ACCESSION(S): PRJNA360163

REPOSITORIES: GEO