biostudies-literatureWang LIntramural NIH HHS1122-30https://www.ebi.ac.uk/biostudies/studies/S-EPMC2805063biostudies-literatureUnknown9(10)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.Nature immunologyDistinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells.PMC2805063Z01 BC010671Z99 CA999999Zhu JBosselut RFowlkes BJWildt KFZhang XTessarollo LFeigenbaum LPaul WEWang LfalseDistinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells.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.2008-01-01T00:00:00Z2008 Oct2026-04-12T15:54:01.035Z2019-03-27T00:27:53ZS-EPMC28050631877690410.1038/ni.1647