Modulation of transcription burst amplitude underpins dosage compensation in the Drosophila embryo

Dosage compensation, the balancing of X linked gene expression between sexes and to the autosomes, is critical to an organisms fitness and survival. In Drosophila, dosage compensation involves hypertranscription of the male X chromosome. Here we use quantitative live imaging and modelling at single-cell resolution to determine the mechanism underlying X chromosome dosage compensation in Drosophila. We show that the four X chromosome genes studied undergo transcriptional bursting in male and female embryos. Mechanistically our data reveal that transcriptional upregulation of male X chromosome genes is primarily mediated by a higher RNA polymerase II initiation rate and burst amplitude across the expression domain. In contrast, burst frequency is spatially modulated in nuclei within the expression domain in response to different transcription factor concentrations to tune the transcriptional response. Together, these data show how the local and global regulation of distinct burst parameters establish the complex transcriptional outputs underpinning developmental patterning.