X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes1. The biochemical mechanisms utilized for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. Lucchesi (1998)2 proposed that MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of MSL complex and MSL-dependent H4K16 acetylation to the bodies of X-linked genes in males, with a bias towards 3′ ends3-7. However, experimental analysis of MSL function at the mechanistic level has been challenging due to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. In this study, we use global run-on sequencing (GRO-seq)8 to examine the specific effect of MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific control may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.