| Autor: |
Ohmura S, Mizuno S, Oishi H, Ku CJ, Hermann M, Hosoya T, Takahashi S, Engel JD |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of clinical investigation [J Clin Invest] 2016 Mar 01; Vol. 126 (3), pp. 865-78. Date of Electronic Publication: 2016 Jan 25. |
| DOI: |
10.1172/JCI83894 |
| Abstrakt: |
The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell-specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte-specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell-regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell-specific transcriptional activity. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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