MSL1 plays a central role in assembly of the MSL complex, essential for dosage compensation in Drosophila

In male Drosophila, histone H4 acetylated at Lys16 is enriched on the X chr omosome, and most X-linked genes are transcribed at a higher rate than in f emales (thus achieving dosage compensation). Five proteins, collectively ca lled the MSLs, are required for dosage compensation and male viability. Her e we show that one of these proteins, MSL1, interacts with three others, MS L2, MSL3 and MOF. The latter is a putative histone acetyl transferase. Over expression of either the N- or C-terminal domain of MSL1 has dominant-negat ive effects, i.e. causes male-specific lethality. The lethality due to expr ession of the N-terminal domain is reduced if msl2 is co-overexpressed, MSL 2 co-purifies over a FLAG affinity column with the tagged region of MSL1, a nd both MSL3 and MOF co-purify with the FLAG-tagged MSL1 C-terminal domain, Furthermore, the MSL1 C-terminal domain binds specifically to a GST-MOF fu sion protein and co-immunoprecipitates with HA-tagged MSL3, The MSL1 C-term inal domain shows similarity to a region of mouse CBP, a transcription co-a ctivator, We conclude that a main role of MSL1 is to serve as the backbone for assembly of the MSL complex.