@article{480719f134544e7d8ad963cca6587f8b,
title = "KDM6B-dependent chromatin remodeling underpins effective virus-specific CD8+ T cell differentiation",
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.",
keywords = "CD8 T cell, chromatin, histone demethylase, T cell activation, T cell memory, virus immunity",
author = "Jasmine Li and Kristine Hardy and Moshe Olshansky and Adele Barugahare and Gearing, {Linden J.} and Prier, {Julia E.} and Sng, {Xavier Y.X.} and Nguyen, {Michelle Ly Thai} and Dana Piovesan and Russ, {Brendan E.} and {La Gruta}, {Nicole L.} and Hertzog, {Paul J.} and Sudha Rao and Turner, {Stephen J.}",
note = "Funding Information: 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. Funding Information: S.R. is currently the founder/chief scientific officer of EpiAxis Therapeutics. This manuscript received no funding from EpiAxis for this work. S.J.T. is a member of the scientific advisory board for Medicago, Inc., QC, Canada. This manuscript received no funding from Medicago for this work. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = mar,
day = "16",
doi = "10.1016/j.celrep.2021.108839",
language = "English",
volume = "34",
pages = "1--22",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}