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

Yi Zhong, Sarah K. Walker, Yuri Pritykin, Christina S. Leslie, Alexander Y. Rudensky, Joris van der Veeken

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)122-134
Number of pages13
JournalNature Immunology
Volume23
Issue number1
DOIs
StatePublished - Jan 2022

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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