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

ABSTRACT: Summary Dosage compensation, the balancing of X-linked gene expression between sexes and to the autosomes, is critical to an organism’s fitness and survival. In Drosophila, dosage compensation involves hypertranscription of the male X chromosome. Here, we use quantitative live imaging and modeling at single-cell resolution to study 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 can establish the complex transcriptional outputs underpinning developmental patterning. Graphical abstract Highlights • MS2 imaging of transcription of dosage-compensated genes at single-cell resolution• X chromosome genes undergo transcriptional bursting in male and female embryos• Dosage-compensated X chromosome genes have higher burst amplitude in male embryos• X chromosome gene transcription is regulated spatially by changes in burst frequency Using live imaging to study transcription of dosage-compensated X chromosome genes at single-cell resolution, Forbes Beadle et al. show that transcriptional bursts have higher amplitude in male embryos compared with females. This gender cue is integrated with transcription factor concentration, which regulates burst frequency, to establish the transcriptional response.

SUBMITTER: Forbes Beadle L 

PROVIDER: S-EPMC10283159 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature