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

Abstract

Specific targeting of the protein complexes formed by the Polycomb group of proteins is critically required to maintain the inactive state of a group of developmentally regulated genes. Although the role of DNA binding proteins in this process has been well established, it is still not understood how these proteins target the Polycomb complexes specifically to their response elements. Here we show that the grainyhead gene, which encodes a DNA binding protein, interacts with one such Polycomb response element of the bithorax complex. Grainyhead binds to this element in vitro. Moreover, grainyhead interacts genetically with pleiohomeotic in a transgene-based, pairing-dependent silencing assay. Grainyhead also interacts with Pleiohomeotic in vitro, which facilitates the binding of both proteins to their respective target DNAs. Such interactions between two DNA binding proteins could provide the basis for the cooperative assembly of a nucleoprotein complex formed in vitro. Based on these results and the available data, we propose that the role of DNA binding proteins in Polycomb group-dependent silencing could be described by a model very similar to that of an enhanceosome, wherein the unique arrangement of protein-protein interaction modules exposed by the cooperatively interacting DNA binding proteins provides targeting specificity.

We are indebted to S. Bray, M. Vidal, R. Tjian, and P. Verrijzer for sharing their fly stocks, cDNA clones, and antibodies. We also thank Anita Kiss and Ildikó Krausz for excellent technical assistance and M. Erdélyi, T. Török, and I. Bajusz for critical reading of the manuscript.

This work was supported by grants from the Hungarian National Science Foundation (T038076) and the National Institutes of Health (3 R01GM043432, subcontract 00000870; H.G.), by the Swiss National Foundation, by the State of Geneva (F.K.), and by a young investigator grant from the Human Frontier Science Program (R.K.M.). A.B. was supported by an EMBO short-term fellowship (ASTF 9705).

We have no competing financial interests.