XSip1 neuralizing activity involves the co-repressor CtBP and occurs through BMP dependent and independent mechanisms

被引:49
作者
van Grunsven, Leo A.
Taelman, Vincent
Michiels, Christine
Verstappen, Griet
Souopgui, Jacob
Nichane, Massimo
Moens, Emmanuelle
Opdecamp, Karin
Vanhomwegen, Jessica
Kricha, Sadia
Huylebroeck, Danny
Bellefroid, Eric J.
机构
[1] Katholieke Univ Leuven VIB, Flanders Interuniv Inst Biotechnol, Dept Dev Biol VIB7, Div Mol & Dev Genet, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven VIB, Lab Mol Biol Celgen, Div Mol & Dev Genet, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven VIB, Dept Human Genet, B-3000 Louvain, Belgium
[4] Univ Libre Bruxelles, Lab Embryol Mol, IBMM, B-6041 Gosselies, Belgium
关键词
BMP4; CtBP; neural induction; Sip1; Sox2; Zfhx1b; ZEB2;
D O I
10.1016/j.ydbio.2007.02.045
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:34 / 49
页数:16
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