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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Binding Sites
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Cell Line
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Enhancer Elements, Genetic / genetics*
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Gene Expression Regulation
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Green Fluorescent Proteins
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Luminescent Proteins / metabolism
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Membrane Proteins / metabolism*
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Mice
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Mice, Transgenic
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Muscle Proteins / chemistry
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Mutation
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Promoter Regions, Genetic
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Notch
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Signal Transduction
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T-Lymphocytes / physiology*
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Transcriptional Activation
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Transfection
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Up-Regulation
Substances
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Antigens, CD
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Luminescent Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Muscle Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Notch
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Smpx protein, mouse
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pre-T cell receptor alpha
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Green Fluorescent Proteins