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Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome. To explore the basis for the sex specificity of dosage compensation, we examined MSL-1 expression in males, females, and dosage compensation mutants. MSL-1 protein levels are negatively regulated by Sxl in females, resulting in male-specific expression of MSL-1. In addition, msl-2 is required for translation and/or stability of MSL-1 in males. Furthermore, the wild-type pattern of MSL-1 localization to the X chromosome is dependent on mle and msl-3 function, although a subset of sites are stained with MSL-1 antibodies in these mutants. Collectively, these data provide the first evidence for an order of msl gene function and suggest that male-specific expression of MSL-1 plays a key role in the sex specificity of dosage compensation.

Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila.