In Drosophila, equal gene expression from the sex chromosomes in males and females (dosage compensation) is achieved by hypertranscription from the single X chromosome in male flies. Furuhashi and colleagues now identify DNA supercoiling factor (SCF), a protein that generates negative supercoils in DNA, as an important player in this process (see p. 4475). They show that SCF knockdown by RNAi causes male-specific reduction of X-linked gene expression and male lethality. SCF, they report, colocalizes along the X chromosome with the male-specific lethality (MSL) complex, which is required for dosage compensation, and overexpression of SCF gives the X chromosome a bloated appearance. This phenotype depends on the MSL component MOF, a histone acetyltransferase, and is suppressed by overexpression of the chromatin remodelling protein ISWI, which antagonizes MOF activity. The researchers conclude that by counteracting ISWI action, SCF helps to form and/or maintain the transcriptionally active open chromatin that is needed for X chromosome hypertranscription in male flies.