The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation

In Drosophila, the MSL complex is required for the dosage compensation of X -linked genes in males and contains a histone acetyltransferase, MOF. A poi nt mutation in the MOF acetyl-CoA-binding site results in male-specific let hality. Yeast Esa1p, a MOF homolog, is essential for cell cycle progression and is the catalytic subunit of the NuA4 acetyltransferase complex. Here w e report that NuA4 purified from yeast with a point mutation in the acetyl- CoA-binding domain of Esa1p exhibits a strong decrease in histone acetyltra nsferase activity, yet has no effect on growth. We demonstrate that Eaf3p ( Esa1p-associated factor-3 protein), a yeast protein homologous to the Droso phila dosage compensation protein MSL3, is also a stable component of the N uA4 complex. Unlike other subunits of the complex, it is not essential, and the deletion mutant has no growth phenotype. NuA4 purified from the mutant strain has a decreased apparent molecular mass, but retains wildtype level s of histone H4 acetyltransferase activity. The EAF3 deletion and the ESA1 mutation lead to a decrease in PHO5 gene expression; the EAF3 deletion also significantly reduces HIS4 and TRP4 expressions. These results, together w ith those previously obtained with both the MSL and NuA4 complexes, undersc ore the importance of targeted histone H4 acetylation for the gene-specific activation of transcription.