Researchers have discovered that DNA in newly fertilized eggs forms a structured 3D scaffold before the genome activates, challenging long-held assumptions. Using a new technique called Pico-C, scientists mapped this organization in fruit fly embryos. A related study shows that disrupting this structure in human cells triggers an immune response as if under viral attack.
For decades, scientists assumed that the DNA in a fertilized egg remained unstructured until the embryo's genes activated, a process known as Zygotic Genome Activation. However, a study published in Nature Genetics overturns this view. Led by Professor Juanma Vaquerizas at the Medical Research Council Laboratory of Medical Sciences, the research reveals that the genome already exhibits a complex 3D organization in the earliest stages of development.
The team developed Pico-C, a sensitive method that maps DNA folding using far less material—about ten times less—than traditional techniques. Applied to fruit fly (Drosophila) embryos, it showed that shortly after fertilization, the DNA forms loops and folds in a modular pattern. This arrangement positions genes for precise regulation, ensuring proper cell function and preventing abnormalities.
"We used to think of the time before the genome awakens as a period of chaos," said Noura Maziak, the lead author. "But by zooming in closer than ever before, we can see that it's actually a highly disciplined construction site. The scaffolding of the genome is being erected in a precise, modular way, long before the 'on' switch is fully flipped."
In fruit flies, embryos divide rapidly in the first few hours post-fertilization, making them ideal for such studies. The findings suggest this early architecture is crucial for development.
A companion study in Nature Cell Biology, conducted by Professor Ulrike Kutay and colleagues at ETH Zürich, examined human cells. Removing molecular anchors like LBR and LAP2 that stabilize the 3D structure caused the genome to collapse. Cells then mistook this for a viral invasion, activating the innate immune system and potentially leading to inflammation and disease.
"These two studies tell a complete story," Vaquerizas noted. "The first shows us how the genome's 3D structure is carefully built at the start of life. The second shows us the disastrous consequences for human health if that structure is allowed to collapse."
The research was funded by the Medical Research Council and the Academy of Medical Sciences. Both studies appeared in 2026.
