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

Cell Rep. 2017 Dec 19;21(12):3624-3636. doi: 10.1016/j.celrep.2017.11.097.

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 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.

Keywords: CD8+ T cell; chromatin; epigenetics; influenza; transcription factor.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • Cell Lineage*
  • Cells, Cultured
  • Enhancer Elements, Genetic*
  • Epigenesis, Genetic
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Influenza, Human / genetics
  • Influenza, Human / metabolism*
  • Mice
  • Mice, Inbred C57BL

Substances

  • Histones