Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway

Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway
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DOI:
10.1101/gad.960702
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发表时间:
2002-02-01
影响因子:
10.5
通讯作者:
Leder, P
Leder, P
中科院分区:
生物学1区
文献类型:
--
作者:
Reizis, B;Leder, P

文献摘要

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Notch 信号通路调节 T 淋巴细胞的定型和早期发育。我们研究了 Notch 介导的前 T 细胞受体 α (pTa) 基因的诱导,该基因是 Notch 的 T 细胞特异性转录靶标。 pTa 增强子由 Notch 信号传导激活,并包含其核效应子 CSL 的结合位点。 CSL 结合位点的突变消除了 Notch 诱导的增强子,并延迟了 T 细胞谱系定型期间 pTa 转基因表达的上调。这些结果显示了哺乳动物 Notch/CSL 信号通路诱导阶段和组织特异性基因的直接机制。
The Notch signaling pathway regulates the commitment and early development of T lymphocytes. We studied Notch-mediated induction of the pre-T cell receptor alpha (pTa) gene, a T-cell-specific transcriptional target of Notch. The pTa enhancer was activated by Notch signaling and contained binding sites for its nuclear effector, CSL. Mutation of the CSL-binding sites abolished enhancer induction by Notch and delayed the up-regulation of pTa transgene expression during T cell lineage commitment. These results show a direct mechanism of stage- and tissue-specific gene induction by the mammalian Notch/CSL signaling pathway.