KDM6B-dependent chromatin remodeling underpins effective virus-specific CD8+ T cell differentiation

Authors:

• 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.

Details:

Cell Reports, Volume 34, Issue 11, 2021-03-16

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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.