The histone acetyltransferase MOF (males-absent-on-the-first) is required for the regulation of X chromosome gene dosage compensation in Drosophila males. In this issue, Kind et al. (2008) show that MOF is also found on autosomes and that it has two modes of binding: one in males for X chromosome dosage compensation and the other in both sexes for X chromosome and autosomal gene regulation independent of dosage compensation.