BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.
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Date
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Publisher
Springer Nature
https://doi.org/10.1038/ni.3441
https://doi.org/10.1038/ni.3441
Abstract
Description
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.
Keywords
Adaptive Immunity, Animals, Basic-Leucine Zipper Transcription Factors, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, Cultured, Enhancer Elements, Genetic, Gene Expression Regulation, Immunologic Memory, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Oncogene Protein p65(gag-jun), Signal Transduction, Transcription Factor AP-1, Vaccinia, Vaccinia virus