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- Title
The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells.
- Authors
Miyazaki, Masaki; Rivera, Richard R; Miyazaki, Kazuko; Lin, Yin C; Agata, Yasutoshi; Murre, Cornelis
- Abstract
It is established that the transcription factor E2A and its antagonist Id3 modulate the checkpoints consisting of the precursor to the T cell antigen receptor (pre-TCR) and the TCR. Here we demonstrate that Id3 expression was higher beyond the pre-TCR checkpoint, remained high in naive T cells and showed a bimodal pattern in the effector-memory population. We show how E2A promoted T lineage specification and how pre-TCR-mediated signaling affected E2A genome-wide occupancy. Thymi in Id3-deficient mice had aberrant development of effector-memory cells, higher expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl-6 and, unexpectedly, T cell-B cell conjugates and B cell follicles. Collectively, our data show how E2A acted globally to orchestrate development into the T lineage and that Id3 antagonized E2A activity beyond the pre-TCR checkpoint to enforce the naive fate of T cells.
- Subjects
T cell receptors; TRANSCRIPTION factors; GENE expression; LABORATORY mice; CHEMOKINES; CELLULAR signal transduction
- Publication
Nature Immunology, 2011, Vol 12, Issue 10, p992
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2086