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XB-ART-10519
J Biol Chem. November 3, 2000; 275 (44): 34365-74.

The homeodomain transcription factor Xvent-2 mediates autocatalytic regulation of BMP-4 expression in Xenopus embryos.

Schuler-Metz A , Knöchel S , Kaufmann E , Knöchel W .


Abstract
Like other genes of the transforming growth factor-beta 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.

PubMed ID: 10938274
Article link: J Biol Chem.

Genes referenced: bmp2 bmp4 chrd.1 gata2 gsc hhex hist1h4d inhba lgals4.2 rpsa ventx1.2 ventx2.1 ventx2.2



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