Abstract
The transcription factors GATA-3 and ThPOK are required for intrathymic differentiation of CD4+ T cells, but their precise functions in this process remain unclear. Here we show that, contrary to previous findings, Gata3 disruption blocked differentiation into the CD4+ T cell lineage before commitment to the CD4+ lineage and in some contexts permitted the 'redirection' of major histocompatibility complex class II–restricted thymocytes into the CD8+ lineage. GATA-3 promoted ThPOK expression and bound to a region of the locus encoding ThPOK established as being critical for ThPOK expression. Finally, ThPOK promoted differentiation into the CD4+ lineage in a way dependent on GATA-3 but inhibited differentiation into the CD8+ lineage independently of GATA-3. We propose that GATA-3 acts as a specification factor for the CD4+ lineage 'upstream' of the ThPOK-controlled CD4+ commitment checkpoint.
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Acknowledgements
We thank Y. Xiong, R. Jenkinson and J. Rozenberg for assistance with ChIP assays; E. Southon for embryonic stem cell recombination; M. Pellegrini and A. Nussenzweig for assistance with recombination-mediated genetic engineering; E. Castro and G. Sanchez for mouse technical assistance; B. Taylor and S. Banerjee for cell sorting; and A. Gégonne and A. Singer for reading the manuscript. Supported by the Intramural Research Programs of the National Cancer Institute, Center for Cancer Research, and of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
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Wang, L., Wildt, K., Zhu, J. et al. Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells. Nat Immunol 9, 1122–1130 (2008). https://doi.org/10.1038/ni.1647
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DOI: https://doi.org/10.1038/ni.1647
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