The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor

We describe a novel mammalian DNA binding activity that requires at least t wo symmetrically methylated CpG dinucleotides in its recognition sequence, preferably within the sequence 5 ' CGCG. A key component of the activity is Kaiso, a protein with POZ and zinc-finger domains that is known to associa te with p120 catenin. We find that Kaiso behaves as a methylation-dependent transcriptional repressor in transient transfection assays. Kaiso is a con stituent of one of two methyl-CpG binding complexes originally designated a s MeCP1. The data suggest that zinc-finger motifs are responsible for DNA b inding, and may therefore target repression to specific methylated regions of the genome. As Kaiso associates with p120 catenin, Kaiso may link events at the cell surface with DNA methylation-dependent gene silencing.