Hierarchical regulation of the resting and activated T cell epigenome by major transcription factor families

Nat Immunol. 2022 Jan;23(1):122-134. doi: 10.1038/s41590-021-01086-x. Epub 2021 Dec 22.


T cell activation, a key early event in the adaptive immune response, is subject to elaborate transcriptional control. In the present study, we examined how the activities of eight major transcription factor (TF) families are integrated to shape the epigenome of naive and activated CD4 and CD8 T cells. By leveraging extensive polymorphisms in evolutionarily divergent mice, we identified the 'heavy lifters' positively influencing chromatin accessibility. Members of Ets, Runx and TCF/Lef TF families occupied the vast majority of accessible chromatin regions, acting as 'housekeepers', 'universal amplifiers' and 'placeholders', respectively, at sites that maintained or gained accessibility upon T cell activation. In addition, a small subset of strongly induced immune response genes displayed a noncanonical TF recruitment pattern. Our study provides a key resource and foundation for the understanding of transcriptional and epigenetic regulation in T cells and offers a new perspective on the hierarchical interactions between critical TFs.

Publication types

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

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Chromatin / immunology
  • Epigenesis, Genetic / immunology
  • Epigenome / immunology*
  • Gene Expression Regulation / immunology
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Transcription Factors / immunology*


  • Chromatin
  • Transcription Factors