Journal article

Distinct Epigenetic Signatures Delineate Transcriptional Programs during Virus-Specific CD8( ) T Cell Differentiation

Brendan E Russ, Moshe Olshanksy, Heather S Smallwood, Jasmine Li, Alice E Denton, Julia E Prier, Angus T Stock, Hayley A Croom, Jolie G Cullen, Michelle LT Nguyen, Stephanie Rowe, Matthew R Olson, David B Finkelstein, Anne Kelso, Paul G Thomas, Terry P Speed, Sudha Rao, Stephen J Turner

IMMUNITY | CELL PRESS | Published : 2014

Abstract

The molecular mechanisms that regulate the rapid transcriptional changes that occur during cytotoxic T lymphocyte (CTL) proliferation and differentiation in response to infection are poorly understood. We have utilized ChIP-seq to assess histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection. Our results show that within naive T cells, codeposition of the permissive H3K4me3 and repressive H3K27me3 modifications is a signature of gene loci associated with gene transcription, replication, and cellular differentiation. Upon differentiation into effector and/or memory CTLs, the majority of these gene l..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by NIH


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

The authors would like to thank Drs. Nicole La Gruta and Peter Doherty for discussion and helpful suggestions. We would also like to thank members of the Australian Genome Research Facility, Parkville, Victoria, for helpful suggestions. 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 A. K. and Project grant #APP1003131 awarded to S.J.T. and S.R.) and NIH grants AI107625 and AI077714 (awarded to P.G.T.). S.J.T. is supported by an Australian Research Council Future Fellowship; The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing.