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Inhibition of EBF function by active Notch signaling reveals a novel regulatory pathway in early B-cell development

By Emma Smith, P Akerblad, T Kadesch, Håkan Axelson and Mikael Sigvardsson

Abstract

The Notch signaling pathway is involved in several lineage commitment and differentiation events. One of these is fate determination of the common lymphoid progenitor, promoting T-cell development at the expense of B-cell differentiation. It has been suggested that this process relies on Notch's ability to inhibit E proteins, which are crucial for early B-cell development. Here, we report that Notch signaling also modulates the function of the transcription factor, early B-cell factor (EBF). Transient transfection of intracellular Notch1 (Notch1-IC) into a pre-B cell line resulted in the down-regulation of EBF-regulated promoters and diminished the capacity of EBF to activate these promoters in an epithelial cell line. This correlated with a reduction in the ability of EBF to bind DNA. Ligand-induced stimulation of endogenous Notch receptors with Delta4 mimicked the activity of Notch1-IC toward EBF. These data suggest that Notch signaling may affect B- versus T-lineage commitment by the targeting of both EBF and E2A

Topics: Hematology
Publisher: 'American Society of Hematology'
Year: 2005
DOI identifier: 10.1182/blood-2004-12-4744
OAI identifier: oai:lup.lub.lu.se:3d954f21-7901-4f3b-a44f-86fcd0a18cfb
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