Efficient and Specific Targeting of Polycomb Group Proteins Requires Cooperative Interaction between Grainyhead and Pleiohomeotic

Specific targeting of the protein complexes formed by the Polycomb group ofproteins is critically required to maintain the inactive state of agroup of developmentally regulated genes. Although the role of DNAbinding proteins in this process has been well established, it is stillnot understood how these proteins target the Polycomb complexesspecifically to their response elements. Here we show that thegrainyhead gene, which encodes a DNA binding protein,interacts with one suchPolycomb response element of thebithorax complex. Grainyhead binds to this element in vitro. Moreover,grainyhead interacts genetically withpleiohomeotic in a transgene-based, pairing-dependent silencing assay. Grainyheadalso interacts with Pleiohomeotic in vitro, which facilitates thebinding of both proteins to their respective target DNAs. Suchinteractions between two DNA binding proteins could provide the basisfor the cooperative assembly of a nucleoprotein complex formed invitro. Based on these results and the available data, we propose thatthe role of DNA binding proteins inPolycomb group-dependentsilencing could be described by a model very similar to that of anenhanceosome, wherein the unique arrangement of protein-proteininteraction modules exposed by the cooperatively interacting DNAbinding proteins provides targetingspecificity.