Transcription factor Zic2 inhibits Wnt-catenin signaling
| Autor: | Pourebrahim, Rasoul, Houtmeyers, Rob, Ghogomu, Stephen M, Janssens, Stefan, Thelie, Aurore, Tran, Hong Thi, Langenberg, Tobias, Vleminck, Kris, Bellefroid, Eric, Cassiman, J J, Tejpar, Sabine |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of biological chemistry, 286 (43 |
| Popis: | The Zic transcription factors play critical roles during embry- onic development. Mutations in the ZIC2 gene are associated with human holoprosencephaly, but the etiology is still unclear. Here, we report a novel function for ZIC2 as a regulator of beta-catenin-TCF4-mediated transcription. We show that ZIC2 can bind directly to the DNA-binding high mobility group box of TCF4 via its zinc finger domain and inhibit the transcrip- tional activity of the beta-catenin-TCF4 complex. However, the binding of TCF4 to DNA was not affected by ZIC2. Zic2 RNA injection completely inhibited beta-catenin-induced axis duplica- tion in Xenopus embryos and strongly blocked the ability of beta-catenin to induce expression of known Wnt targets in animal caps. Moreover, Zic2 knockdown in transgenic Xenopus Wnt reporter embryos led to ectopic Wnt signaling activity mainly at the midbrain-hindbrain boundary. Together, our results dem- onstrate a previously unknown role for ZIC2 as a transcriptional regulator of the beta-catenin-TCF4 complex. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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