3D genome structure forms before gene activation in early embryos

A three-dimensional (3D) structure of DNA begins forming before an embryo's own genes switch on.

Researchers from the MRC Laboratory of Medical Sciences (LMS) in London, together with collaborators in Zurich, Switzerland, examined the 3D structure of DNA in fruit fly embryos and mammalian cells. The spatial organisation of DNA plays an important role in genome regulation, helping determine which genes are switched on or off. In a study published in Nature Genetics, the team found that a defined 3D genome structure begins to form in the embryo before zygotic genome activation – the timepoint in development when an embryo's own genes start to become active.

'We used to think of the time before the genome awakens as a period of chaos,' explained Noura Maziak, PhD student at LMS, and first author of the fruit fly study. '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.'

These findings were supported by a second study using human and mouse cells, published in Nature Cell Biology which reported similar findings, suggesting that related processes may also occur in mammalian cells. The researchers found that disrupting these DNA structures in human cells triggered the innate immune system and impaired the cells' ability to develop correctly during processes such as embryogenesis and cell differentiation.

'These two studies tell a complete story,' said Professor Juanma Vaquerizas, corresponding author of the fruit fly paper, '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 discoveries were made possible by the development of a new method that enables high-resolution mapping of the genome's 3D structure. The technique could help researchers better understand inflammatory diseases, and may offer insights into regenerative medicine and cancer.