Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8(+) T cell differentiation

Immunity. 2014 Nov 20;41(5):853-65. doi: 10.1016/j.immuni.2014.11.001. Epub 2014 Nov 6.


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 loci lose repressive H3K27me3 while retaining the permissive H3K4me3 modification. In contrast, immune-related effector gene promoters within naive T cells lacked the permissive H3K4me3 modification, with acquisition of this modification occurring upon differentiation into effector/memory CTLs. Thus, coordinate transcriptional regulation of CTL genes with related functions is achieved via distinct epigenetic mechanisms.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • DNA Methylation / genetics
  • Epigenesis, Genetic / immunology*
  • Histones / genetics*
  • Immunologic Memory
  • Influenza A virus / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology
  • Protein Processing, Post-Translational
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transcription, Genetic / immunology


  • Histones