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Originally published In Press as doi:10.1074/jbc.M201831200 on April 18, 2002

J. Biol. Chem., Vol. 277, Issue 26, 23872-23881, June 28, 2002
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Cooperative Interaction of Xvent-2 and GATA-2 in the Activation of the Ventral Homeobox Gene Xvent-1B*

Henner Friedle and Walter KnöchelDagger

From the Abteilung Biochemie, Universität Ulm, Albert-Einstein Allee 11, Ulm 89081, Germany

The Xvent family of homeobox transcription factors is essential for the establishment of the dorsal-ventral body axis during Xenopus embryogenesis. In contrast to Xvent-2B and other members of the Xvent-2 subfamily, Xvent-1B is not a direct response gene of bone morphogenetic protein-4 signaling. Xvent-1B is activated by Xvent-2, but CHX experiments revealed the requirement of additional factors. In this study, we report on the cooperative effect of Xvent-2 and the zinc finger transcription factor GATA-2 on the promoter of the Xvent-1B gene. We show that GATA-2 is a direct target gene of bone morphogenetic protein-4 and that GATA-2 interacts with Xvent-2 to activate transcription of Xvent-1B. Both transcription factors bind to distinct elements within the Xvent-1B promoter, and GATA-2 physically interacts with the C-terminal domain of Xvent-2. Promoter/reporter studies in Xenopus embryos revealed that full activation of Xvent-1B requires both Xvent-2 and GATA-2. Moreover, the two factors are sufficient to direct transcription of Xvent-1B in the presence of CHX at the ventral side of the embryo. The failure of both factors to activate Xvent-1B on the dorsal side suggests the existence of a dorsal inhibitor. This inhibitor is likely a component of the dorsal Wnt signaling pathway because nuclear translocation of beta -catenin before midblastula transition results in a suppression of Xvent-1B transcription.

* This work was supported by Deutsche Forschungsgemeinschaft Grant SFB497/A1 and by Fonds der Chemischen Industrie.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. Tel.: 49-731-502-3280; Fax: 49-731-502-3277; E-mail: walter.knoechel@medizin.uni-ulm.de.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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