Journal
CELL REPORTS
Volume 34, Issue 11, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.108839
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Funding
- National Health and Medical Research Council of Australia [5671222, APP1003131]
- Australian Research Council [DP DP170102020]
- NHMRC Principal Research Fellowship
- Australian Research Council Future Fellowship
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New research has revealed that rapid upregulation of the histone demethylase KDM6B is crucial for initiating H3K27me3 removal and promoting T cell differentiation and proliferation after CD8(+) T cell activation. Inhibiting KDM6B-dependent H3K27me3 demethylation limits the effectiveness of primary virus-specific CD8(+) T cell response and the formation of memory CD8(+) T cell populations. The study defines early spatial and temporal events necessary for chromatin reprogramming in CD8(+) T cells for autonomous proliferation and differentiation.
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.
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