XSip1 neuralizing activity involves the co-repressor CtBP and occurs through BMP dependent and independent mechanisms
| Autor: | Jessica Vanhomwegen, Danny Huylebroeck, Sadia Kricha, Griet Verstappen, Jacob Souopgui, Emmanuelle Moens, Eric Bellefroid, Vincent Taelman, Christine Michiels, Leonardus Van Grunsven, Massimo Nichane, Karin Opdecamp |
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| Přispěvatelé: | Liver Cell Biology, Cell Biology and Histology |
| Rok vydání: | 2007 |
| Předmět: |
Xenopus
Sox2 Repressor BMP4 Bone Morphogenetic Protein 4 Xenopus Proteins Biology Bone morphogenetic protein Nervous System Zfhx1b Neural induction SOX2 Ectoderm Animals CtBP Promoter Regions Genetic Molecular Biology Transcription factor Psychological repression ZEB2 Homeodomain Proteins Regulation of gene expression Gene Expression Regulation Developmental Cell Biology biology.organism_classification Molecular biology Protein Structure Tertiary Cell biology DNA-Binding Proteins Repressor Proteins Alcohol Oxidoreductases Bone Morphogenetic Proteins Sip1 Epidermis Neural development Developmental Biology |
| Zdroj: | Vrije Universiteit Brussel |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2007.02.045 |
| Popis: | The DNA-binding transcription factor Smad-interacting protein-1 (Sip1) (also named Zfhx1b/ZEB2) plays essential roles in vertebrate embryogenesis. In Xenopus, XSip1 is essential at the gastrula stage for neural tissue formation, but the precise molecular mechanisms that underlie this process have not been fully identified yet. Here we show that XSip1 functions as a transcriptional repressor during neural induction. We observed that constitutive activation of BMP signaling prevents neural induction by XSip1 but not the inhibition of several epidermal genes. We provide evidence that XSip1 binds directly to the BMP4 proximal promoter and modulates its activity. Finally, by deletion and mutational analysis, we show that XSip1 possesses multiple repression domains and that CtBPs contribute to its repression activity. Consistent with this, interference with XCtBP function reduced XSip1 neuralizing activity. These results suggest that Sip1 acts in neural tissue formation through direct repression of BMP4 but that BMP-independent mechanisms are involved as well. Our data also provide the first demonstration of the importance of CtBP binding in Sip1 transcriptional activity in vivo. |
| Databáze: | OpenAIRE |
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