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- Title
Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling.
- Authors
Seiler, Michael P; Mathew, Rebecca; Liszewski, Megan K; Spooner, Chauncey; Barr, Kenneth; Meng, Fanyong; Singh, Harinder; Bendelac, Albert
- Abstract
Interactions driven by the T cell antigen receptor (TCR) determine the lineage fate of CD4+CD8+ thymocytes, but the molecular mechanisms that induce the lineage-determining transcription factors are unknown. Here we found that TCR-induced transcription factors Egr2 and Egr1 had higher and more-prolonged expression in precursors of the natural killer T (NKT) than in cells of conventional lineages. Chromatin immunoprecipitation followed by deep sequencing showed that Egr2 directly bound and activated the promoter of Zbtb16, which encodes the NKT lineage-specific transcription factor PLZF. Egr2 also bound the promoter of Il2rb, which encodes the interleukin 2 (IL-2) receptor ?-chain, and controlled the responsiveness to IL-15, which signals the terminal differentiation of the NKT lineage. Thus, we propose that persistent higher expression of Egr2 specifies the early and late stages of NKT lineage differentiation, providing a discriminating mechanism that enables TCR signaling to 'instruct' a thymic lineage.
- Subjects
TRANSCRIPTION factors; GENE expression; CELL differentiation; T cells; KILLER cells; CELLULAR signal transduction; THYMOCYTES; MOLECULAR biology
- Publication
Nature Immunology, 2012, Vol 13, Issue 3, p264
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2230