Chromatin accessibility of CD8 T cell differentiation and metabolic regulation

Cell Biol Toxicol. 2021 Jun;37(3):367-378. doi: 10.1007/s10565-020-09546-0. Epub 2020 Jul 12.

Abstract

CD8+T cells play an important role in controlling infections and tumorigenesis in vivo. naïve CD8+T cells exponentially expand and exert effector functions in response to TCR ligation. After antigen clearance, most effector CD8+T cells (Teff) experience activation-induced cell death, only a small portion becomes long-lived memory T cells (Tmem). The cell-intrinsic mechanisms driving the differentiation need further understanding. Here we used combined transposase-accessible chromatin (ATAC-seq) technology and RNA-seq analysis to explore chromatin accessibility in CD8+T cell subsets (naïve T cells, Teff, and Tmem). The data demonstrates different chromatin openness of CD8+T cell states is associated with metabolic regulation and the high accessibility of upstream binding site SP1 emerged as critical transcription factor for both Teff and Tmem in fatty acid oxidation (FAO) and glycolysis. The different presence of accessible regions in CD8+T cell subsets provides a novel perspective for understanding epigenetic mechanisms underlying T cell differentiation and related immune response.

Keywords: CD8 T cell; Chromatin accessibility; Epigenetic regulation; Metabolism; SP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Differentiation / genetics*
  • Chromatin / genetics*
  • Chromatin Immunoprecipitation Sequencing / methods
  • Humans
  • Infections / genetics
  • Infections / pathology
  • RNA-Seq / methods
  • Sp1 Transcription Factor / genetics*
  • Transposases / genetics*

Substances

  • Chromatin
  • Sp1 Transcription Factor
  • SP1 protein, human
  • Transposases