Zelda orchestrates Drosophila early zygotic-genome activation

In all animals, embryogenesis is first controlled by the maternal gene products that are deposited into the oocyte during oogenesis. Later, the control will be transferred to the zygotic genome in a process called maternal-to-zygotic transition (MZT). To ensure that development progresses appropriately during the MZT, two important processes are involved: maternal mRNA and protein degradation, and zygotic genome activation. In this thesis, we focused on zygotic genome activation.;A long-standing question has been whether a specific transcriptional activator is responsible for zygotic genome activation. ten Bosch et al. (2006) reported that a common heptamer (TAGGTAG) and related sequences (the TAGteam sequences), are over-represented upstream of pre-cellular blastoderm genes, and the sequences are important for their expression. This implies there may be a dedicated transcription factor that interacts with the TAGteam sites to activate the early genes.;By using yeast-one-hybrid screening, we identified Zelda, which is encoded by CG12701, and binds to TAGteam sites specifically. We generated null mutants to confirm zelda is responsible for the TAGteam genes' activation. We also compared the expression profiles of wild type embryos and zelda mutants. The results showed that zelda affects 75% of the early genes, and suggests Zelda is a key activator during the MZT in Drosophila.;We also mapped the Zelda bound regions in vivo by ChIP-chip and found Zelda binds to about 2000 regions in Drosophila genome during MZT. We identified many more Zelda target genes in the early embryo than our initial profiling suggested, and revealed that Zelda is integral to all early gene networks. From analyzing the changes in gene expression of the dorsoventral (DV) and anteriorposterior (AP) patterning genes in zelda mutant embryos, we found that Zelda cooperates with morphogens to establish patterning gene expression domains. We suggest that Zelda orchestrates Drosophila early zygotic-genome activation by regulating gene expression in all dimensions, temporally and spatially.