trans-homolog interaction regulates the sex-biased expression of an X-linked gene

Sex-biased gene expression patterns in animals are generally controlled by the somatic sex-determination hierarchies. How the different tiers of these hierarchies act on sexually dimorphic gene regulation is still poorly understood. In the developing Drosophila biarmipes wing, the X-linked gene yellow is expressed in males in a specific distal spot pattern that prefigures a corresponding adult pigmentation pattern. This yellow expression pattern is controlled by the spot enhancer, but the origin of yellow sexually dimorphic expression is unknown. Here we find that the functional interaction between homologous yellow alleles silences specifically the spot enhancer, which is therefore active in males (XY) but not in females (XX). We show that inserting yellow at homologous positions on autosomes recapitulates, in either sex, the homologous-dependent silencing of the spot enhancer. We further find that this silencing requires the yellow intron as well as the architectural protein Mod(mdg4). Finally, we show that Mod(mdg4) is also necessary for the sex-biased expression of some X-linked genes in the brain. Our results demonstrate that regulatory interactions between X-linked homologous alleles promote their sex-biased expression, independently of the canonical sex-determination hierarchy. More generally, they illustrate the biological significance of homologous chromosome pairing and trans-homolog interactions for the sexually dimorphic regulation of X-linked genes.