“Jump Start and Gain” Model for Dosage Compensation in Drosophila Based on Direct Sequencing of Nascent Transcripts

Dosage compensation in Drosophila is mediated by the MSL complex, which increases male X-linked gene expression approximately 2-fold. The MSL complex preferentially binds the bodies of active genes on the male X, depositing H4K16ac with a 3' bias. Two models have been proposed for the influence of the MSL complex on transcription: one based on promoter recruitment of RNA polymerase II (Pol II), and a second featuring enhanced transcriptional elongation. Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation. We also compare X and autosomes from published data on paused and elongating polymerase in order to assess the role of Pol II recruitment. Our results support a model for differentially regulated elongation, starting with release from 5' pausing and increasing through X-linked gene bodies. Our results highlight facilitated transcriptional elongation as a key mechanism for the coordinated regulation of a diverse set of genes.