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Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling.
- Source :
-
Nature Immunology . Mar2012, Vol. 13 Issue 3, p264-271. 8p. 1 Chart, 7 Graphs. - Publication Year :
- 2012
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15292908
- Volume :
- 13
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Nature Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 71818467
- Full Text :
- https://doi.org/10.1038/ni.2230