Suppression of heterochromatic gene variegation can be used to distinguish and characterize E(var) genes potentially important for chromosome structure in Drosophila melanogaster.

Hundreds of genic modifiers of position effect variegation (PEV) have been isolated in Drosophila melanogaster with a view to identifying genes important for chromosome structure. Here we propose a supplementary genetic screen to pinpoint candidate genes that are most likely to function in chromosome organization, within the enhancer of variegation [E(var)] class of modifiers. Our strategy takes advantage of the fact that variegating euchromatic and heterochromatic genes respond oppositely to changes in the dosage of heterochromatin proteins. Consequently, only when enhancement of euchromatic gene variegation results from increased formation of heterochromatin should suppression of heterochromatic gene variegation be observed. Mutations in four E(var) genes were tested for the ability to suppress variegation of multiple alleles of the heterochromatic light ( lt) gene in a variety of tissues and at several developmental stages. Mutations in E(var)3-4, E(var)3-5 and modifier of mdg4 [ mod(mdg4)] suppressed lt variegation. In contrast, a mutation in the Trithorax-like ( Trl) gene, which encodes GAGA factor, enhanced or had no effect on lt variegation, consistent with its known role in promoting transcription. These data show that suppression of lt variegation can be used as an assay to distinguish between members of the E(var) class of modifiers.