The N-Terminal Region of Drosophila MSL1 Interacts with Zinc Finger Proteins and Promotes the Recruitment of the MSL Complex to the X Chromosome in Males

The Drosophila protein male-specific lethal 1 (MSL1) is part of the five-subunit male-specific lethal (MSL) complex that binds only to the X chromosome in males. MSL1 contains a 93-amino-acid N-terminal unstructured region followed by a coiled-coil domain that forms a homodimer. The MSL1 dimer and male-specific lethal 2 (MSL2), which interacts with its coiled-coil domain, form a core that is primarily responsible for the specific recruitment of the MSL complex to X-chromosome high-affinity sites (HASs). In a yeast two-hybrid analysis, we found that the N-terminal region of MSL1, primarily amino acids 66–85 and the coiled-coil domain, interacts with many DNA-binding transcription factors. The coiled-coil domain of Drosophila virilis MSL1 (vCC) retains the ability to interact with Drosophila melanogaster MSL2 but not with zinc finger proteins. Expression of a double mutant of MSL1 (MSL1Δ20vCC), in which amino acids 66–85 (Δ20) have been deleted and the coiled-coil domain has been replaced with the vCC domain, significantly reduced dosage compensation in males due to decreased binding of the MSL complex to the X chromosome. Substitution of MSL1 with MSL1vCC in females ectopically expressing MSL2 also significantly reduced recruitment of the MSL complex to the X chromosome. Altogether, these results indicate a key role of the N-terminal region of MSL1 not only in the assembly of the MSL complex but also in its recruitment to the X chromosome in males.