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

Publication date: 19 December 2017
Source:Cell Reports, Volume 21, Issue 12
Author(s): Brendan E. Russ, Moshe Olshansky, Jasmine Li, Michelle L.T. Nguyen, Linden J. Gearing, Thi H.O. Nguyen, Matthew R. Olson, Hayley A. McQuilton, Simone Nüssing, Georges Khoury, Damian F.J. Purcell, Paul J. Hertzog, Sudha Rao, Stephen J. Turner
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 subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8⁺ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation.

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Teaser

Russ et al. demonstrate that a subset of poised transcriptional enhancers found in naive virus-specific CD8⁺ T cells acquire a non-canonical chromatin signature upon differentiation. These data provide the genomic location for T cell lineage-specific transcription factor binding that is necessary for virus-specific T cell differentiation.


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