Linking Global Histone Acetylation to the Transcription Enhancement of X-chromosomal Genes in Drosophila Males

It has become well established for several genes that targeting of histone acetylation to promoters is required for the activation of transcription. In contrast, global patterns of acetylation have not been ascribed to any particular regulatory function. In Drosophila , a specific modification of H4, acetylation at lysine 16, is enriched at hundreds of sites on the male X chromosome due to the activity of the male-specific lethal (MSL) dosage compensation complex. Utilizing chromatin immunoprecipitation, we have determined that H4Ac16 is present along the entire length of X-linked genes targeted by the MSL complex with relatively modest levels of acetylation at the promoter regions and high levels in the middle and/or 3′ end of the transcription units. We propose that global acetylation by the MSL complex increases the expression of X-linked genes by facilitating transcription elongation rather than by enhancing promoter accessibility. We have also determined that H4Ac16 is absent from a region of the X chromosome that includes a gene known to be dosage-compensated by a MSL-independent mechanism. This study represents the first biochemical interpretation of the very large body of cytological observations on the chromosomal distribution of the MSL complex.