Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs
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Abstract
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.
Journal
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- The journal of clinical investigation
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The journal of clinical investigation 126 (3), 865-878, 2016-03
The American Society for Clinical Investigation
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Keywords
Details 詳細情報について
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- CRID
- 1050282677616937600
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- NII Article ID
- 120007129597
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- NII Book ID
- AA00695520
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- DOI
- 10.1172/jci83894
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- ISSN
- 15588238
- 00219738
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- HANDLE
- 2241/00138696
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN