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Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3'. Promotes floor plate development and prechordal plate development. Required for lens development as early as the stage of lens field ...[+]
Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3'. Promotes floor plate development and prechordal plate development. Required for lens development as early as the stage of lens field formation, partly through regulation of gene expression of the cell cycle inhibitor cdknx/p27(xic1). Required for formation of the neural crest downstream of multiple signaling pathways, and acts at the neural plate border via both DNA-binding dependent and independent mechanisms; acts in a DNA-binding dependent manner to repress pro-apoptotic and neural crest differentiation genes, including id3, delta1, and cdknx/p27(xic1), and thus promote the cell survival of neural plate border cells and maintain them in an undifferentiated state. Represses transcription of id3, at least in part through the repression of bmp4. On the other hand, acts in a DNA-independent manner separate from the transcriptional repressor function, to stimulate cell proliferation and promote neural crest formation. Via this DNA-independent route, acts in neurulae upstream of stat3 to transiently up-regulate the notch ligand dll1/delta1, which in turn up-regulates id3 expression. Then interacts directly with id3, which blocks the transcriptional repressor function of hes4-B/hairy2b to allow the progression of neural crest progenitors through specification and differentiation. Also acts via repressor-dependent and repressor-independent mechanisms in early gastrulae to establish the prospective anterior prechordal mesoderm identity in the Spemann organizer; induces specific genes independently from direct transcriptional regulation, and represses the genes specific for neighboring tissues through direct transcriptional repression. Modulates lateral inhibition during notch signaling and regulates the cell context dependent effects of notch (which can have inhibitory, permissive or enhancing roles in muscle or neural differentiation). Inhibits myogenesis. [-]