KDM6B-dependent chromatin remodelling underpins effective virus-specific CD8+ T cell differentiation.
Li, J.; Hardy, K.; Olshansky, M.; Barugahare, A.; Gearing, L. J.; Prier, J. E.; Sng, X. Y.; Nguyen, M. L. T.; Piovesan, D.; Russ, B. E.; La Gruta, N. L.; Hertzog, P.; Rao, S.; Turner, S. J.
10.1101/2020.02.03.933218 bioRxivShow abstract
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 profiled 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 first cell division was required for initiating H3K27me3 removal at genes essential for subsequent T cell differentiation and proliferation. Inhibition of KDM6B-dependent H3K27me3 demethylation limited 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 spatio-temporal events underpinning early lineage-specific epigenetic reprogramming that is necessary for autonomous CD8+ T cell proliferation and differentiation.
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