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J. Biol. Chem., Vol. 275, Issue 44, 34365-34374, November 3, 2000
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From the Abteilung Biochemie, Universität Ulm,
Albert-Einstein-Allee 11, D-89081 Ulm, Germany
Like other genes of the transforming growth
factor-
The Homeodomain Transcription Factor Xvent-2 Mediates
Autocatalytic Regulation of BMP-4 Expression in Xenopus
Embryos*
,,
family, the BMP-4 gene is regulated by an
autocatalytic loop. In Xenopus embryos this loop can be
ectopically induced by injection of BMP-2 RNA. However, cycloheximide
treatment subsequent to BMP-2 overexpression revealed that BMP
signaling is not direct but requires additional factor(s). As putative
mediator we have identified Xvent-2 which is activated by BMP-2/4
signaling and, in turn, activates BMP-4 transcription.
Using promoter/reporter assays we have delineated Xvent-2 responsive
elements within the BMP-4 gene. We further demonstrate that
Xvent-2 which has recently been characterized as a transcriptional
repressor can also act, context dependent, as an activator binding two
copies of a 5'-CTAATT-3' motif in the second intron of the
BMP-4 gene. Replacement of Xvent-2 target sites within the
goosecoid (gsc) promoter by the
BMP-4 enhancer converts Xvent-2 caused repression of
gsc to strong activation. This switch is obviously due to
adjacent nucleotides probably binding a transcriptional co-activator
interacting with Xvent-2. A model is presented describing the mechanism
of BMP-4 gene activation in Xenopus embryos at
the early gastrula stage.
*
This work was supported by Deutsche Forschungsgemeinschaft
Grants Kn 200/4-6 and SFB 497/A1 and the 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.
Contributed equally to the results of this work.
§
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 © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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