EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming

Nat Commun. 2019 Jul 24;10(1):3306. doi: 10.1038/s41467-019-11233-6.

Abstract

Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8+ T cell innate memory program.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Core Binding Factor Alpha 3 Subunit / immunology
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Core Binding Factor Alpha 3 Subunit / physiology*
  • DNA Helicases / immunology
  • DNA Helicases / metabolism
  • DNA Helicases / physiology*
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling
  • Immunologic Memory*
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • Transcription Factors / immunology
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Eomes protein, mouse
  • Nuclear Proteins
  • Runx3 protein, mouse
  • T-Box Domain Proteins
  • Transcription Factors
  • Smarca4 protein, mouse
  • DNA Helicases