Self-association of the Drosophila zeste protein is responsible for transvection effects

The zeste gene product is required for transvection effects that imply the ability of regulatory elements on one chromosome to affect the expression of the homologous gene in a somatically paired chromosome. The z¹ mutation causes a pairing dependent inhibition of the expression of the white gene. Both of these phenomena can be explained by the tendency of zeste protein, expressed in bacteria or in flies, to self-associate, forming complexes of several hundred monomers. These large aggregates bind to DNA and are found in nuclear matrix preparations, probably because they co-sediment with the matrix. The principal determinants of this self-association are located in the C-terminal half of the protein but some limited aggregation is obtained also with the N-terminal half, which contains the DNA binding domain. The z¹ and z(op6) mutant proteins aggregate to the same degree as the wild type but the z(11G3) product, a pseudorevertant of z¹, has a reduced tendency to aggregate. This mutation, wich in vivo is antagonistic to z¹ and does not support transvection effects, can be made to revert its phenotype when the mutant protein is overproduced under the control of the heat shock promoter. These results indicate that both the zeste-white interaction and transvection effects require the formation of high order aggregates. When the z¹ protein is overproduced in vivo, it reduces the expression of an unpaired copy of white, indicating that the normal requirement for chromosome pairing is simly a device to increase the size of the aggregate bound to the white regulatory region.