Histone H4 isoforms can be found at four different lysine residues, acetylated in different combinations. When polytene chromsomes from Drosophila larva are examined with antisera specific for each of the four acetylated lysine residues, differently acetylated isoforms are found in distinct patterns of distribution. H4 molecules acetylated at lysines 5 and 8 are distributed in overlapping, but nonidentical islands throughout the euchromatic chromosome arms, suggesting that H4 acetylated at lysines 5 and 8 is associated with transcriptionally active genes. H4 acetylated at lysine 16 is found at numerous sites along the transcriptionally hyperactive X chromosome in male larvae, but not in male autosomes or any chromosome in female cells. The association of H4 acetylated at lysine 16 with male X chromosomes is intimately related to the process of dosage compensation.
Males have only one X chromosome, compared with the two found in females.
Were male X chromosomes to function at the same level of transcriptional activation as females, males would have only half the level of X chromosome coded gene products as females. Histone H4 plays a role in dosage compensation. The specifically acetylated isoform of histone H4, H4Ac16, is detected predominantly on the male X chromosome. No H4HAc16 is found on X chromosomes in mutants of MSL genes. Control of gene accessability to transcription factors is not the only role of acetylation of H4 in the biology of the cell.