Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway.
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.
Reizis
Boris
B
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Leder
Philip
P
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051880:Receptors, Notch; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
D015703:Antigens, CD; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051880:Receptors, Notch; C499035:Smpx protein, mouse; C090377:pre-T cell receptor alpha; D049452:Green Fluorescent Proteins