The nuclear to cytoplasmic ratio directly regulates zygotic transcription in Drosophila

Early embryos must rapidly generate large numbers of cells to form an organism. Many species accomplish this through a series of rapid, reductive, and transcriptionally silent cleavage divisions. Previous work has demonstrated that before both cell cycle elongation and zygotic genome activation (ZGA), the number of divisions is regulated by the ratio of nuclear content to cytoplasm (N/C). To understand how the N/C ratio affects the timing of ZGA we directly assayed the behavior of several previously identified N/C-ratio-dependent genes using the MS2-MCP reporter system in living Drosophila embryos with altered ploidy and cell cycle time. For every gene that we examined, we found that transcription is delayed in haploids. The N/C ratio influences transcription through two separate modes of action. For many genes the effect of ploidy can be entirely accounted for by changes in cell cycle duration. However, for a subset of genes the N/C ratio directly affects the probability of transcription initiation. While it appears that cell cycle duration is the dominant component in modulating transcription for most genes, our data demonstrate that the regulatory elements of at least some genes respond directly to the N/C-ratio, independent of interphase length.