Thpok-independent repression of Runx3 by Gata3 during CD4+ T-cell differentiation in the thymus

Eur J Immunol. 2013 Apr;43(4):918-28. doi: 10.1002/eji.201242944. Epub 2013 Feb 12.


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 promotes Cd4 expression in Thpok-deficient thymocytes. Thus, in addition to its previously documented role in promoting CD4-lineage gene-expression, Gata3 represses CD8-lineage gene expression. These findings identify Gata3 as a critical pivot of CD4-CD8 lineage differentiation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Binding Sites
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism*
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Core Binding Factor Alpha 3 Subunit
  • GATA3 Transcription Factor
  • Th-POK protein, mouse
  • Transcription Factors