The protein encoded by the Drosophila position‐effect variegation suppressor gene Su(var)3‐9 combines domains of antagonistic regulators of homeotic gene complexes.

Modifier mutations of position‐effect variegation (PEV) represent a useful tool for a genetic and molecular dissection of genes connected with chromatin regulation in Drosophila. The Su(var)3‐9 gene belongs to the group of haplo suppressor loci which manifest a triplo enhancer effect. Mutations show a strong suppressor effect even in the presence of PEV enhancer mutations, indicating a central role of this gene in the regulation of PEV. By molecular analysis, Su(var)3‐9 could be correlated with a 2.4 kb transcript which encodes a putative protein of 635 amino acids containing a chromo domain and a region of homology to Enhancer of zeste and trithorax, two antagonistic regulators of the Antennapedia and Bithorax gene complexes, as well as to the human protein ALL‐1/Hrx which is implicated in acute leukemias. This region of homology is found in all four proteins at the C‐terminus. The homology of Su(var)3‐9 to both negative (Polycomb and Enhancer of zeste) and positive (trithorax) regulators of the Antennapedia and Bithorax complexes also suggests similarities in the molecular processes connected with stable transmission of a determined state and the clonal propagation of heterochromatinization.