Molecular characterization of the male-specific lethal-3 gene and investigations of the regulation of dosage compensation in Drosophila.

In Drosophila, dosage compensation occurs by transcribing the single male X chromosome at twice the rate of each of the two female X chromosomes. This hypertranscription requires four autosomal male-specific lethal (msl) genes and is negatively regulated by the Sxl gene in females. Two of the msls, the mle and msl-1 genes, encode proteins that are associated with hundreds of specific sites along the length of the male X chromosome. MLE and MSL-1 X chromosome binding are negatively regulated by Sxl in females and require the functions of the other msls in males. To investigate further the regulation of dosage compensation and the role of the msls in this process, we have cloned and molecularly characterized another msl, the msl-3 gene. We have found that MSL-3 is also associated with the male X chromosome. We have further investigated whether Sxl negatively regulates MSL-3 X-chromosome binding in females and whether MSL-3 X-chromosome binding requires the other msls. Our results suggest that the MLE, MSL-1 and MSL-3 proteins may associate with one another in a male-specific heteromeric complex on the X chromosome to achieve its hypertranscription.