Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila

Significance The posttranslational modification of nucleosomes is implicated in the regulation of gene expression and chromatin packaging in all eukaryotes. In this study, we investigate the function of histone H4 lysine 16 (H4K16) and its acetylation in Drosophila by generating strains in which lysine 16 is mutated to arginine, glutamine, or alanine. The main conclusion of our paper is that even though H4K16 acetylation was reported to be a critical regulator of chromatin folding in vitro and has therefore been assumed to affect many different nuclear processes, its essential function in Drosophila is in one process: X-chromosome dosage compensation in males.