The homeodomain transcription factor Xvent-2 mediates autocatalytic regulation of BMP-4 expression in Xenopus embryos.
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.
Schuler-Metz
A
A
Abteilung Biochemie, Universität Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
Knöchel
S
S
Kaufmann
E
E
Knöchel
W
W
D000818:Animals; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA; D018983:DNA Footprinting; D017931:DNA Primers; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D007438:Introns; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors; D015533:Transcriptional Activation; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C099992:ventx2.1 protein, Xenopus; D004247:DNA