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The Drosophila melanogaster Polycomb group protein Posterior Sex Combs is a component of Polycomb repressive complex 1 and is central to Polycomb group-mediated silencing. A related Polycomb group gene, Suppressor 2 of zeste, is thought to be partially redundant in function. The two proteins share a small region of homology but also contain regions of unconserved sequences. Here we report a biochemical characterization of Suppressor 2 of zeste. Like Posterior Sex Combs, Suppressor 2 of zeste binds DNA, compacts chromatin, and inhibits chromatin remodeling. Interestingly, the regions of the two proteins responsible for these activities lack sequence homology. Suppressor 2 of zeste can also replace Posterior Sex Combs in a functional complex with other Polycomb group proteins, but unlike with their biochemical activities, complex formation is mediated by the region of Suppressor 2 of zeste that is homologous to that of Posterior Sex Combs. Our results establish Suppressor 2 of zeste as a functional homolog of Posterior Sex Combs and suggest that the two proteins operate via similar molecular mechanisms.