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

Authors:

• Russ, Brendan E.
• Olshansky, Moshe
• Li, Jasmine
• Nguyen, Michelle L.T.
• Gearing, Linden J.
• Nguyen, Thi H.O.
• Olson, Matthew R.
• McQuilton, Hayley A.
• Nüssing, Simone
• Khoury, Georges
• Purcell, Damian F.J.
• Hertzog, Paul J.
• Rao, Sudha
• Turner, Stephen J.

Details:

Cell Reports, Volume 21, Issue 12, 2017-12-19

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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.