Abstract

Memory T cells are characterized by their ability to exhibit a rapid response to the recall antigen. Our previous study shows that histone methylation provides a chromatin basis for the rapid transcriptional response of memory CD8 T cells. To further understand how the histone methylation patterns are established and maintained in memory T cells, we conducted a parallel analysis of gene expression changes with histone methylation changes in naïve and memory (central and effector memory cells) CD8 T cells after in vitro stimulation. Naïve and memory CD8 T cells were isolated from normal adult and stimulated in vitro with antibodies against CD3 and CD28. Gene expression changes (microarray) and histone methylation (H3K4me3 and H3K27me3) (ChIP-Seq) were analyzed. We observed substantial changes in gene expression (~25% increase and ~25% decrease of total expressed genes) after 72 hours of stimulation. Similar trends of histone methylation (H3K4me3 and H3K27me3) changes in corresponding genes in CD8 T cells were observed, suggesting a dynamic change of histone methylation in CD8 T cells after activation. Furthermore, we found that the open chromatin of some poised genes in memory CD8 T cells were established in activated naïve CD8 T cells. Together, these results indicate that histone methylation is dynamic after activation in CD8 T cells and suggest that activation-induced change of chromatin in naïve T cells is part of differentiation process to establish memory T cells.

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