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

Cell Rep. 2023 Apr 25;42(4):112382. doi: 10.1016/j.celrep.2023.112382. Epub 2023 Apr 14.

Abstract

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.

Keywords: CP: Molecular biology; Drosophila embryo; MS2; RNA polymerase II; X chromosome; burst amplitude; dosage compensation; live imaging; transcriptional bursting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dosage Compensation, Genetic
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila* / genetics
  • Drosophila* / metabolism
  • Female
  • Male
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • X Chromosome / metabolism

Substances

  • Drosophila Proteins
  • Transcription Factors