Natural Genetic Variation Reveals Key Features of Epigenetic and Transcriptional Memory in Virus-Specific CD8 T Cells

Immunity. 2019 May 21;50(5):1202-1217.e7. doi: 10.1016/j.immuni.2019.03.031. Epub 2019 Apr 23.


Stable changes in chromatin states and gene expression in cells of the immune system form the basis for memory of infections and other challenges. Here, we used naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to explore the mechanisms underlying long-lasting versus transient gene regulation in CD8 T cells responding to acute viral infection. Stably responsive DNA elements were characterized by dramatic and congruent chromatin remodeling events affecting multiple neighboring sites and required distinct transcription factor (TF) binding motifs for their accessibility. Specifically, we found that cooperative recruitment of T-box and Runx family transcription factors to shared targets mediated stable chromatin remodeling upon T cell activation. Our observations provide insights into the molecular mechanisms driving virus-specific CD8 T cell responses and suggest a general mechanism for the formation of transcriptional and epigenetic memory applicable to other immune and non-immune cells.

Keywords: epigenetic; memory; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Line
  • Chromatin / genetics
  • Chromatin Assembly and Disassembly / genetics*
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Epigenesis, Genetic / genetics
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics*
  • Gene Expression Regulation / immunology
  • Genetic Variation
  • Immunologic Memory / genetics
  • Immunologic Memory / immunology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • T-Box Domain Proteins / genetics*
  • Transcription, Genetic / genetics


  • Chromatin
  • Core Binding Factor Alpha 2 Subunit
  • Runx1 protein, mouse
  • T-Box Domain Proteins