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

Jasmine Li, Kristine Hardy, Moshe Olshansky, Adele Barugahare, Linden J. Gearing, Julia E. Prier, Xavier Y.X. Sng, Michelle Ly Thai Nguyen, Dana Piovesan, Brendan E. Russ, Nicole L. La Gruta, Paul J. Hertzog, Sudha Rao, Stephen J. Turner

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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 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.

Original languageEnglish
Article number108839
Pages (from-to)1-22
Number of pages22
JournalCell Reports
Volume34
Issue number11
DOIs
Publication statusPublished - 16 Mar 2021

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