BACH2 regulates CD8 + T cell differentiation by controlling access of AP-1 factors to enhancers

Rahul Roychoudhuri, David Clever, Peng Li, Yoshiyuki Wakabayashi, Kylie M Quinn, Christopher A. Klebanoff, Yun Ji, Madhusudhanan Sukumar, Robert L. Eil, Zhiya Yu, Rosanne Spolski, Douglas C. Palmer, Jenny H. Pan, Shashank J. Patel, Derek C. Macallan, Giulia Fabozzi, Han Yu Shih, Yuka Kanno, Akihiko Muto, Jun ZhuLuca Gattinoni, John J. O'Shea, Klaus Okkenhaug, Kazuhiko Igarashi, Warren J. Leonard, Nicholas P. Restifo

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72 Citations (Scopus)

Abstract

T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8 + T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. In naive cells, this prevented TCR-driven induction of genes associated with terminal differentiation. Upon effector differentiation, reduced expression of BACH2 and its phosphorylation enabled unrestrained induction of TCR-driven effector programs.

Original languageEnglish
Pages (from-to)851-860
Number of pages10
JournalNature Immunology
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2016
Externally publishedYes

Keywords

  • adaptive immunity
  • gene regulation in immune cells
  • immunological memory
  • transcription factors

Cite this

Roychoudhuri, R., Clever, D., Li, P., Wakabayashi, Y., Quinn, K. M., Klebanoff, C. A., Ji, Y., Sukumar, M., Eil, R. L., Yu, Z., Spolski, R., Palmer, D. C., Pan, J. H., Patel, S. J., Macallan, D. C., Fabozzi, G., Shih, H. Y., Kanno, Y., Muto, A., ... Restifo, N. P. (2016). BACH2 regulates CD8 + T cell differentiation by controlling access of AP-1 factors to enhancers. Nature Immunology, 17(7), 851-860. https://doi.org/10.1038/ni.3441