Abstract
Maternally deposited factors play a crucial role in initiating zygotic transcription. However, the mechanisms by which maternal factors regulate early zygotic transcript diversity through alternative splicing remain unclear. Furthermore, how early in development widespread sex-specific transcript diversity occurs is not known. We show that widespread sex-specific transcript diversity occurs much earlier than previously thought and present a new pipeline called time2splice to quantify splicing changes over time. Using the powerful Drosophila model, we define several mechanisms by which a maternal factor regulates sex-specific zygotic transcriptome diversity: 1) In both males and females, GA-binding pioneer factor CLAMP (Chromatin linked adapter for MSL proteins) links the DNA of gene bodies of sex-specifically spliced genes directly to the RNA of target genes and physically interacts with snRNA and protein components of the splicing machinery; 2) In males, CLAMP regulates the distribution of the spliceosome component Maleless (MLE) to prevent aberrant sex-specific splicing; 3) In females, CLAMP binds to the DNA and RNA encoded by the sxl gene, the master regulator of sex determination, to directly regulate its splicing which also modulates downstream targets. Overall, we provide key insight into how maternal factors influence sex-specific transcript diversity.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵Ω contributed equally