Distinct 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.
Wang
Lie
L
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Wildt
Kathryn F
KF
Zhu
Jinfang
J
Zhang
Xianyu
X
Feigenbaum
Lionel
L
Tessarollo
Lino
L
Paul
William E
WE
Fowlkes
B J
BJ
Bosselut
Rémy
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism
D050990:GATA3 Transcription Factor; D014157:Transcription Factors; C494748:Gata3 protein, mouse; C497211:Zbtb7b protein, mouse
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