Journal article

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 YX Sng, Michelle Ly Thai Nguyen, Dana Piovesan, Brendan E Russ, Nicole L La Gruta, Paul J Hertzog, Sudha Rao, Stephen J Turner

CELL REPORTS | CELL PRESS | Published : 2021

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..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council


Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia (program grant 5671222 awarded to awarded to S.J.T. and N.L.L. and project grant APP1003131 awarded to S.J.T.) and an Australian Research Council Discovery grant (DP DP170102020 awarded to S.J.T. and S.R.); S.J.T. is supported by an NHMRC Principal Research Fellowship; and N.L.L. is supported by an Australian Research Council Future Fellowship. We thank the Monash Genomics Platform (Micromon) for high-throughput sequencing and the Monash Bioinformatics Platform for data analysis.