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 β-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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Seiler MP,Mathew R,Liszewski MK,Spooner CJ,Barr K,Meng F,Singh H,Bendelac Adoi
10.1038/ni.2230subject
Has Abstractpub_date
2012-02-05 00:00:00pages
264-71issue
3eissn
1529-2908issn
1529-2916pii
ni.2230journal_volume
13pub_type
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