The transcriptional repressor Kaiso is reported to bind both methylated DNA and non-methylated CTGCNA motifs and is known to be important for development because morpholino knockdown of Kaiso developmentally delays Xenopusembryos during gastrulation. But which DNA binding mode underpins this phenotype? On ,Richard Meehan and colleagues reveal that the main role of Kaiso in Xenopus development is associated with its ability to bind methylated DNA. They demonstrate that the CTGCNA-binding function of Kaiso is not evolutionarily conserved, whereas the methyl-CpG-binding function is; this property is also sufficient to rescue the gastrulation phenotype in Kaiso-depleted embryos. Furthermore, these embryos show no change in the expression of key Wnt signalling target genes, which Kaiso's CTGCNA-binding function has been proposed to regulate. In a companion paper(), the researchers show that Kaiso instead has the potential to perturb Wnt signalling directly by interacting with the Wnt transducer Tcf3, and suggest that this results in the mutual inhibition of the respective DNA-binding functions of Kaiso and Tcf3.
