Transposable elements, which are found throughout the tree of life, are thousands of fragments of ancient viral DNA that make up more than half of our genomes. Previously disregarded as the “dark side” of the genome, scientists from Ludwig-Maximilians-Universität (LMU) and Helmholtz Munich have now demonstrated their critical function in the early stages of embryonic development.
During the initial hours and days after fertilization, transposable elements—remaining pieces of old viral DNA—reactivate. Although embryonic cells exhibit amazing adaptability at this dynamic stage of early development, it is still unknown what molecular mechanisms and variables govern this plasticity. Although studies conducted on mice and other models indicate that transposable elements are essential for cellular plasticity, it is yet unknown if this trait applies to other mammalian species. These viral leftovers’ varied evolutionary histories cast doubt on their ability to persist across mammalian genomes. Determining the basic principles of genome regulation and improving reproductive medicine depends on an understanding of the regulatory mechanisms controlling the activation of transposable elements.
In order to investigate these ancient DNA sequences, a group of researchers from Helmholtz Munich and LMU, coordinated by Prof. Maria-Elena Torres-Padilla, devised a novel technique to examine their transcription. By comparing embryos from a variety of mammalian species, including mice, cows, pigs, rabbits, and the non-human primate rhesus macaque, they produced a single-embryo atlas. Surprisingly, the researchers found that mammalian embryos re-express very old viral components that were previously believed to be extinct. Additionally, they discovered that different forms of these elements are expressed by each species under study.
These findings demonstrate that transposable element activation is similar across animals, and pinpointing certain elements offers intriguing chances to simultaneously control hundreds of genes in cells.
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,
Our work highlights the importance of understanding the regulatory principles behind transposable elements.
Dr. Marlies Oomen
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. 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.
Prof. Torres-Padilla
Source: Helmholtz Munich
Journal Reference: Marlies E. Oomen, Diego Rodriguez-Terrones, Mayuko Kurome, Valeri Zakhartchenko, Lorenza Mottes, Kilian Simmet, Camille Noll, Tsunetoshi Nakatani, Carlos Michel Mourra-Diaz, Irene Aksoy, Pierre Savatier, Jonathan Göke, Eckhard Wolf, Henrik Kaessmann, Maria-Elena Torres-Padilla. An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development. Cell, 2025; DOI: 10.1016/j.cell.2024.12.013.
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