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  • Title: Xvent-1 mediates BMP-4-induced suppression of the dorsal-lip-specific early response gene XFD-1' in Xenopus embryos.
    Author: Friedle H, Rastegar S, Paul H, Kaufmann E, Knöchel W.
    Journal: EMBO J; 1998 Apr 15; 17(8):2298-307. PubMed ID: 9545242.
    Abstract:
    Ectopic expression of the ventralizing morphogen BMP-4 (bone morphogenetic protein-4) in the dorsal lip (Spemann organizer) of Xenopus embryos blocks transcription of dorsal-lip-specific early response genes. We investigated the molecular mechanism underlying the BMP-4-induced inhibition of the fork head gene XFD-1'. The promoter of this gene contains a BMP-triggered inhibitory element (BIE) which prevents activation of this gene at the ventral/vegetal side of the embryo in vivo. In the present study, we show that BMP-4-induced inhibition is not direct but indirect, and is mediated by Xvent homeobox proteins. Micro-injections of Xvent-1 RNA and XFD-1' promoter deletion mutants demonstrate that Xvent-1 mimics the effect of BMP-4 signalling not only by suppression of the XFD-1' gene, but also by utilizing the BIE. Suppression could be reverted using a dominant-negative Xvent-1 mutant. The repressor domain was localized to the N-terminal region of the protein. Gel-shift and footprint analyses prove that Xvent-1 binds to the BIE. Moreover, PCR-based target-site selection for the Xvent-1 homeodomain confirms distinct motifs within the BIE as preferential binding sites. Thus, biological and molecular data suggest that Xvent-1 acts as direct repressor for XFD-1' transcription and mediates BMP-4-induced inhibition.
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