Ancient viral DNA plays crucial role in early embryo development

Remnants of ancient viral DNA, known as transposable elements, are involved in regulating the start of gene expression during mammalian embryonic development, a study suggests.

Researchers from the Institute of Epigenetics and Stem Cells, Helmholtz Munich, Germany, aimed to understand gene regulation at the earliest stage of development. Previous research in mice suggested that transposable elements play a vital role in the way cells adapt and change but it is uncertain whether this is true in all mammalian species. The researchers developed a new method with more sensitivity and coverage of the genome, and used it to characterise five mammalian species; mouse, cow, pig, rabbit, and a rhesus monkey.

'Our research uncovered that transposable element activation is a distinctive feature of early embryos in several mammalian species. This finding is significant because these early-stage cells can differentiate into all body cell types,' said Professor Maria-Elena Torres-Padilla, corresponding author of the study published in Cell.

The study focused on embryonic genome activation, a key event during development which marks the start of transcription from the embryo. Before then, development is controlled by maternal genetic material. The mechanism controlling the initial transcription of thousands of genes at this precise time is not completely understood. By creating a single-embryo atlas from these different species, researchers discovered that transposable elements, including DNA transposons (see BioNews 1262), are also transcribed at this stage.

'Around half of the mouse and human genome is composed of transposable elements and their remnants, since many transposable elements have become fragmented over evolutionary timescales,' the authors explained in the paper. DNA transposons are not well studied because they are considered extinct. However, this study found both shared and species-specific expression of these DNA sequences, suggesting they have a role at this stage and it is common among mammals.

This stage of development is characterised by great plasticity, which is the ability of the cells to change and adapt to new information. Embryonic cells are totipotent, meaning they can become any cell type. The team suggests that this work provides a resource to improve our understanding of the first wave of embryonic transcription and the start of gene expression which influences development, differentiation and growth.

'This approach offers a novel way to influence cell fate, such as directing stem cell differentiation, which typically requires the simultaneous manipulation of hundreds of genes,' said co-first author Dr Marlies Oomen.

Professor Torres-Padilla explained the implications for early development: 'By understanding how these cells regulate ancient viral elements, we gain crucial insights into the mechanisms of cellular plasticity. This study sets the stage for future research into specific regulatory elements, with broad implications for health, disease, and how manipulating these elements could impact cellular processes.'

In humans, embryonic genomic activation starts right after fertilisation (see BioNews 1127). Future studies characterising human embryos will be needed to demonstrate if transposable elements also play a role in the initiation of transcription for our species.