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Primary sex-determination "switches" evolve rapidly, but Doublesex (DSX)-related transcription factors (DMRTs) act downstream of these switches to control sexual development in most animal species. Drosophila dsx encodes female- and male-specific isoforms (DSX(F) and DSX(M)), but little is known about how dsx controls sexual development, whether DSX(F) and DSX(M) bind different targets, or how DSX proteins direct different outcomes in diverse tissues. We undertook genome-wide analyses to identify DSX targets using in vivo occupancy, binding site prediction, and evolutionary conservation. We find that DSX(F) and DSX(M) bind thousands of the same targets in multiple tissues in both sexes, yet these targets have sex- and tissue-specific functions. Interestingly, DSX targets show considerable overlap with targets identified for mouse DMRT1. DSX targets include transcription factors and signaling pathway components providing for direct and indirect regulation of sex-biased expression.

Original publication




Journal article


Dev Cell

Publication Date





761 - 773


Animals, Animals, Genetically Modified, Binding Sites, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Female, Gene Expression Profiling, Gene Expression Regulation, Gene Expression Regulation, Developmental, Genome, Genome-Wide Association Study, Male, Mice, Phenotype, RNA Interference, Sequence Analysis, DNA, Sex Factors, Transcription Factors