Li Jasmine, Hardy Kristine, Olshansky Moshe, Barugahare Adele, Gearing Linden J, Prier Julia E, Sng Xavier Y X, Nguyen Michelle Ly Thai, Piovesan Dana, Russ Brendan E, La Gruta Nicole L, Hertzog Paul J, Rao Sudha, Turner Stephen J
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Epigenetics and Transcription Laboratory Melanie Swan Memorial Translational Centre, Sci-Tech, University of Canberra, Bruce, ACT 2617, Australia.
Cell Rep. 2021 Mar 16;34(11):108839. doi: 10.1016/j.celrep.2021.108839.
Naive CD8 T cell activation results in an autonomous program of cellular proliferation and differentiation. However, the mechanisms that underpin this process are unclear. Here, we profile genome-wide changes in chromatin accessibility, gene transcription, and the deposition of a key chromatin modification (H3K27me3) early after naive CD8 T cell activation. Rapid upregulation of the histone demethylase KDM6B prior to the first cell division is required for initiating H3K27me3 removal at genes essential for subsequent T cell differentiation and proliferation. Inhibition of KDM6B-dependent H3K27me3 demethylation limits the magnitude of an effective primary virus-specific CD8 T cell response and the formation of memory CD8 T cell populations. Accordingly, we define the early spatiotemporal events underpinning early lineage-specific chromatin reprogramming that are necessary for autonomous CD8 T cell proliferation and differentiation.
初始CD8 T细胞的激活会导致细胞增殖和分化的自主程序。然而，支撑这一过程的机制尚不清楚。在这里，我们描绘了初始CD8 T细胞激活后早期全基因组范围内染色质可及性、基因转录以及一种关键染色质修饰（H3K27me3）沉积的变化。在第一次细胞分裂之前，组蛋白去甲基化酶KDM6B的快速上调是在后续T细胞分化和增殖所必需的基因上启动H3K27me3去除所必需的。抑制KDM6B依赖的H3K27me3去甲基化会限制有效的原发性病毒特异性CD8 T细胞反应的强度以及记忆CD8 T细胞群体的形成。因此，我们定义了早期谱系特异性染色质重编程的早期时空事件，这些事件是CD8 T细胞自主增殖和分化所必需的。
