par 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
Référence The Journal of biological chemistry, 286, 43, page (37732-37740)
Publication Publié, 2011
;Tran, Hong Thi;Langenberg, Tobias;Vleminck, Kris;Bellefroid, Eric ;Cassiman, J J;Tejpar, SabineRéférence The Journal of biological chemistry, 286, 43, page (37732-37740)
Publication Publié, 2011
Article révisé par les pairs
| Résumé : | 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. |
