title: Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling.
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 bind directly to the DNA-binding high mobility group 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 the β-catenin·TCF4 complex.
authors: Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors: Rasoul
authors: R
authors: Pourebrahim
authors: Rob
authors: R
authors: Houtmeyers
authors: Stephen
authors: S
authors: Ghogomu
authors: Sylvie
authors: S
authors: Janssens
authors: Aurore
authors: A
authors: Thelie
authors: Hong Thi
authors: HT
authors: Tran
authors: Tobias
authors: T
authors: Langenberg
authors: Kris
authors: K
authors: Vleminckx
authors: Eric
authors: E
authors: Bellefroid
authors: Jean-Jacques
authors: JJ
authors: Cassiman
authors: Sabine
authors: S
authors: Tejpar
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000382:microbiology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; C491812:ZIC2 protein, human; D051176:beta Catenin