The role of genes with bivalent chromatin in memory CD8 T cells (IRM4P.496)

Abstract

Genes containing both histone methylation H3K4me3 and H3K27me3 markers at the promoter are so called bivalent genes that have been implicated in stem cell differentiation and function. Our previous study identified several dozen bivalent genes in memory CD8 T cells (central memory, TCM and effector memory, TEM). But the role of bivalent genes in CD8 T cells is not understood. Our current focus is to determine the characteristics and functions of these bivalent genes during CD8 memory T cell activation. We used freshly isolated TCM and TEM from human blood that were stimulated by anti-CD3 plus anti-CD28 in vitro, and analyzed histone methylation and mRNA levels of these bivalent genes in resting and activated CD8 memory T cells. Our preliminary results showed that the bivalent status of most genes was stable but corresponding mRNA change was more detectable. We also identified a few bivalent genes whose status changed to become “monovalent”; either H3K4me3 or H3K27me3 after activation. We plan to determine the functional role of these bivalent genes that are altered after activation, and whether the bivalent histone methylation is present on a single gene allele or on two different alleles by sequential ChIP. Our study will shed new insight into the details of histone methylation on gene loci and the function of these bivalent genes in memory CD8 T cells. “This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging “