Journal article

Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8 T Cell-Lineage-Specific Function

BE Russ, M Olshansky, J Li, MLT Nguyen, LJ Gearing, THO Nguyen, MR Olson, HA McQuilton, S Nüssing, G Khoury, DFJ Purcell, PJ Hertzog, S Rao, SJ Turner

Cell Reports | CELL PRESS | Published : 2017

Abstract

Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs), we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs) differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+) chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subs..

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Grants

Awarded by National Genealogical Society


Funding Acknowledgements

The authors would like to thank Drs. Nicole La Gruta and Colby Zaph for discussion and helpful suggestions. We would also like to acknowledge the support of the Micromon Sequencing platform at Monash University for NGS services. This work was supported by grants from the National Health and Medical Research Council of Australia (program grant #5671222 awarded to S.J.T. and project grant #APP1003131 awarded to S.J.T. and S.R.). S.J.T. is supported by an NHMRC Principal Research Fellowship.