Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20

Life Sci Alliance. 2023 Jul 6;6(9):e202201683. doi: 10.26508/lsa.202201683. Print 2023 Sep.

Abstract

Members of the BTB-ZF transcription factor family regulate the immune system. Our laboratory identified that family member Zbtb20 contributes to the differentiation, recall responses, and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were up-regulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. In addition, memory CD8 T cells lacking Zbtb20 were characterized by open chromatin regions with overrepresentation of AP-1 transcription factor motifs and elevated RNA- and protein-level expressions of the corresponding AP-1 components. Finally, we describe motifs and genomic annotations from the DNA targets of Zbtb20 in CD8 T cells identified by cleavage under targets and release under nuclease (CUT&RUN). Together, these data establish the transcriptional and epigenetic networks contributing to the control of CD8 T cell responses by Zbtb20.

Publication types

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

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Cell Differentiation / genetics
  • Chromatin / genetics
  • Chromatin / metabolism
  • Gene Expression Regulation*
  • Transcription Factor AP-1* / genetics
  • Transcription Factor AP-1* / metabolism

Substances

  • Transcription Factor AP-1
  • Chromatin