Activation of transcription through histone H4 acetylation by MOF, an acetyltransferase essential for dosage compensation in Drosophila

Dosage compensation in Drosophila involves a P-fold increase in transcripti on from the single male X relative to the two female X chromosomes. Regulat ion at the level of the chromosome involves alterations in chromatin organi zation: male X chromosomes appear decondensed and are marked by acetylation of histone H4 at lysine 16. We demonstrate that MOF, a protein required fo r dosage compensation with significant sequence similarity to the MYST fami ly of acetyltransferases, is a histone acetyltransferase that acetylates ch romatin specifically at histone H4 lysine 16. This acetylation relieves chr omatin-mediated repression of transcription in vitro and in vivo if MOF is targeted to a promoter by fusion to a DNA-binding domain. Acetylation of ch romatin by MOF, therefore, appears to be causally involved in transcription al activation during dosage compensation.