Setting the stage for development: the maternal-to-zygotic transition in Drosophila.

The zygote has a daunting task ahead of itself; it must develop from a single cell (fertilized egg) into a fully functioning adult with a multitude of different cell types. In the beginning, the zygote has help from its mother, in the form of gene products deposited into the egg, but eventually, it must rely on its own resources to proceed through development. The transfer of developmental control from the mother to the embryo is called the maternal-to-zygotic transition (MZT).

Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation.

Chromatin accessibility is integral to the process by which transcription factors (TFs) read out cis-regulatory DNA sequences, but it is difficult to differentiate between TFs that drive accessibility and those that do not. Deep learning models that learn complex sequence rules provide an unprecedented opportunity to dissect this problem. Using zygotic genome activation in Drosophila as a model, we analyzed high-resolution TF binding and chromatin accessibility data with interpretable deep learning and performed genetic validation experiments.

Enhancer architecture and chromatin accessibility constrain phenotypic space during Drosophila development.

Developmental enhancers bind transcription factors and dictate patterns of gene expression during development. Their molecular evolution can underlie phenotypical evolution, but the contributions of the evolutionary pathways involved remain little understood. Here, using mutation libraries in Drosophila melanogaster embryos, we observed that most point mutations in developmental enhancers led to changes in gene expression levels but rarely resulted in novel expression outside of the native pattern.

Shadow enhancers modulate distinct transcriptional parameters that differentially effect downstream patterning events.

Transcription in the early Drosophila blastoderm is coordinated by the collective action of hundreds of enhancers. Many genes are controlled by so-called 'shadow enhancers', which provide resilience to environment or genetic insult, allowing the embryo to robustly generate a precise transcriptional pattern. Emerging evidence suggests that many shadow enhancer pairs do not drive identical expression patterns, but the biological significance of this remains unclear.

Spatial organization of transcribing loci during early genome activation in Drosophila.

The early Drosophila embryo provides unique experimental advantages for addressing fundamental questions of gene regulation at multiple levels of organization, from individual gene loci to the entire genome. Using 1.5-h-old Drosophila embryos undergoing the first wave of genome activation, we detected ∼110 discrete "speckles" of RNA polymerase II (RNA Pol II) per nucleus, two of which were larger and localized to the histone locus bodies (HLBs).