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Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling

(2011) JOURNAL OF BIOLOGICAL CHEMISTRY. 286(43). p.37732-37740
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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 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 transcriptional 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 duplication 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 demonstrate a previously unknown role for ZIC2 as a transcriptional regulator of the beta-catenin.TCF4 complex.
Keywords
EMBRYONIC STEM-CELLS, BETA-CATENIN, XENOPUS-LAEVIS, POLY(ADP-RIBOSE) POLYMERASE-1, WNT, GENE, TRANSACTIVATION, DIFFERENTIATION, ACTIVATION, EXPRESSION

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Citation

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Chicago
Pourebrahim, Rasoul, Rob Houtmeyers, Stephen Ghogomu, Sylvie Janssens, Aurore Thelie, Hong Tran Thi, Tobias Langenberg, et al. 2011. “Transcription Factor Zic2 Inhibits Wnt/β-catenin Protein Signaling.” Journal of Biological Chemistry 286 (43): 37732–37740.
APA
Pourebrahim, R., Houtmeyers, R., Ghogomu, S., Janssens, S., Thelie, A., Tran Thi, H., Langenberg, T., et al. (2011). Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(43), 37732–37740.
Vancouver
1.
Pourebrahim R, Houtmeyers R, Ghogomu S, Janssens S, Thelie A, Tran Thi H, et al. Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling. JOURNAL OF BIOLOGICAL CHEMISTRY. 2011;286(43):37732–40.
MLA
Pourebrahim, Rasoul, Rob Houtmeyers, Stephen Ghogomu, et al. “Transcription Factor Zic2 Inhibits Wnt/β-catenin Protein Signaling.” JOURNAL OF BIOLOGICAL CHEMISTRY 286.43 (2011): 37732–37740. Print.
@article{1960374,
  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 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 transcriptional 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 duplication 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 demonstrate a previously unknown role for ZIC2 as a transcriptional regulator of the beta-catenin.TCF4 complex.},
  author       = {Pourebrahim, Rasoul and Houtmeyers, Rob and Ghogomu, Stephen and Janssens, Sylvie and Thelie, Aurore and Tran Thi, Hong and Langenberg, Tobias and Vleminckx, Kris and Bellefroid, Eric and Cassiman, Jean-Jacques and Tejpar, Sabine},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  language     = {eng},
  number       = {43},
  pages        = {37732--37740},
  title        = {Transcription factor Zic2 inhibits Wnt/\ensuremath{\beta}-catenin protein signaling},
  url          = {http://dx.doi.org/10.1074/jbc.M111.242826},
  volume       = {286},
  year         = {2011},
}

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