MSL-1 protein is 1,039 amino acids (aa) long; however, the amino acid sequence offers few clues as to its biochemical function (Palmer et al. 1993). Recently, detailed evolutionary and sequence analysis has shown that it contains two conserved domains. There is a putative leucine zipper in the N-ter-minus, and the C-terminus contains a novel PEHE domain with an unknown function (Marin 2003). In addition, MSL-1 has an acidic region and an S/T/P-rich region in its N-terminus (Palmer et al. 1993; Scott et al. 2000). The role of these regions is also unknown.

In yeast two-hybrid assays, MSL-1 residues 85-186 are required for interaction with the RING finger of MSL-2 (Copps et al. 1998). Residues 760-1,039 mediate MSL-1 interaction with MSL-3 in vivo and in vitro. The C-terminal region of MSL-1 has also been shown to interact with MOF in vivo (Scott et al. 2000). MSL-1 can also be co-immunoprecipitated with MSL-2, MSL-3 and MLE from SL2 cells (Kelley et al. 1995; Copps et al. 1998). Overexpression of C- or N-terminal fragments of MSL-1 leads to delocalization of the MSL complex from the X chromosome and male-specific lethality. In particular, the FA84 construct with an 84-aa N-terminal deletion, which still interacts with MSL-2 but fails to localize the X chromosome, caused male-specific lethality. This could be enhanced by deletion of one copy of MSL-2 or suppressed by overexpression of MSL-2. These results suggest that the N-terminus of MSL-1 is important for its targeting to the X chromosome in vivo (Scott et al. 2000).

The MSL complex initially nucleates on approximately 35 'high affinity' or 'chromatin entry' sites, and then spreads to the surrounding chromatin in cis, coating the male X chromosome (Fig. 1B; Lyman et al. 1997; Kelley et al. 1999). Nucleation and spreading processes can be genetically separated. Based on genetic evidence, MSL-1 forms the core dosage compensation complex together with MSL-2. The MSL complex is unable to nucleate on the X chromosome without MSL-1 protein (Lyman et al. 1997). Chang and Kuroda (1998) have suggested that the role of MSL-1 is to tether the MSL complex to chromatin, while MSL-2 regulates sex specificity of dosage compensation and targeting to the X chromosome. The msl-1 gene is transcribed in both sexes, but its translation is partly inhibited by the Sex-lethal protein in females. MSL-1 is also regulated at the level of protein stability. It is unstable in MSL-2 mutants, and if MSL-2 is ectopically expressed in females, MSL-1 protein is stabilized (Chang and Kuroda 1998).

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