Citation:
J Biol Chem. 2011 Sep 9. [Epub ahead of print]
Abstract:
The Zic transcription factors play critical roles during embryonic 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 β-catenin/TCF4-mediated transcription. We show that ZIC2 can directly bind to the DNA-binding HMG-box of TCF4 via its zinc finger domain and inhibit the transcriptional activity of the β-catenin/TCF4 complex. However, the binding of TCF4 to DNA was not affected by ZIC2. Zic2 RNA injection completely inhibited β-catenin-induced axis duplication in Xenopus embryos and strongly blocked the ability of β-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 demonstrate a previously unknown role for ZIC2 as a transcriptional regulator of β-catenin/TCF4 complex.
Organism or Cell Type:
Xenopus laevis
Delivery Method:
Microinjection