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CD4⁺ helper T cells are essential for immune responses and differentiate in the thymus from CD4⁺CD8⁺ “double‐positive” (DP) thymocytes. The transcription factor Runx3 inhibits CD4⁺ T‐cell differentiation by repressing Cd4 gene expression; accordingly, Runx3 is not expressed in DP thymocytes or developing CD4⁺ T cells. The transcription factor Thpok is upregulated in CD4‐differentiating thymocytes and required to repress Runx3. However, how Runx3 is controlled at early stages of CD4⁺ T‐cell differentiation, before the onset of Thpok expression, remains unknown. Here we show that Gata3, a transcription factor preferentially and transiently upregulated by CD4⁺ T‐cell precursors, represses Runx3 and binds the Runx3 locus in vivo. Accordingly, we show that high‐level Gata3 expression and expression of Runx3 are mutually exclusive. Furthermore, whereas Runx3 represses Cd4, we show that Gata3 …