Polycomb group (PcG) proteins participate in the maintenance of transcriptionally repressed state of genes relevant to cell differentiation. Here, we show anterior homeotic transformations of the axial skeleton of YY1(+/-) mice. We find that the penetrance of some of these alterations was reduced in mice that are deficient in the class II PcG gene Ring1/Ring1A, indicating a genetic interaction between those two genes. Further support for this interaction is an abnormal anterior eye formation in Ring1-deficient mice, which is enhanced in compound YY1(+/-)Ring1(-/-) mice. In addition, YY1 forms complexes with Ring1 and other class II PcG proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells. These findings provide evidence for a PcG function for YY1 in vertebrates.