哺乳动物Notch信号通路直接诱导T淋巴细胞特异性基因表达。
Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway.
作者信息
Reizis Boris, Leder Philip
机构信息
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Genes Dev. 2002 Feb 1;16(3):295-300. doi: 10.1101/gad.960702.
Abstract
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.
摘要
Notch信号通路调节T淋巴细胞的定向分化和早期发育。我们研究了Notch介导的前T细胞受体α（pTa）基因的诱导，pTa基因是Notch的T细胞特异性转录靶点。pTa增强子被Notch信号激活，并含有其核效应因子CSL的结合位点。CSL结合位点的突变消除了Notch对增强子的诱导作用，并延迟了T细胞谱系定向分化过程中pTa转基因表达的上调。这些结果显示了哺乳动物Notch/CSL信号通路对阶段和组织特异性基因诱导的直接机制。
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