Gene expression control by transposable elements

Mice use a handful of transposable elements – non-coding repetitive sequences in genomes – to regulate gene expression during the early stages of development.
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A mouse embryo at the early stages of development. Image credit: Miguel Branco

Much of what is known about genetics has come from studying only a tiny fraction of the genome’s sequence, the part that primarily codes for proteins. But the genome has many other features outside these regions, some of which play an important biological role. Transposable elements – repetitive sequences that are present in many species – make up around half of the mouse genome. They are ‘selfish’ elements, in that the spread of them within the genome does not necessarily benefit the host organism. But sometimes transposable elements can be ‘domesticated’, and used to the host’s advantage. For example, transposable elements can generate new genes. In other cases, their non-coding sequences can regulate the activity of other nearby genes or even those elsewhere in the genome.

It remains unclear to what extent transposable elements have shaped genome regulation throughout evolution. One idea is that the spread of transposable elements can help to establish large regulatory networks – whereby many genes are collectively regulated to produce a specific output. But it has not been fully explored how effective transposable elements are at regulating gene expression. Now, Todd et al. investigate whether particular transposable elements, that are suspected to boost the activity of other genes, are essential for normal gene expression in early mouse development.

Todd et al. genetically edited stem cells from the inner and outer layer of the early mouse embryo to find transposable elements that promote gene expression. Whilst some transposable elements were found to be important for gene regulation, not all of the candidates tested were needed to maintain expression levels. To widen the search, several transposable elements were turned off simultaneously by compacting specific stretches of DNA so that they could no longer be activated. When 34 transposable elements were inactivated at once, it emerged that only three transposable elements had a significant impact on gene expression. These findings suggest that whether or not a given transposable element regulates gene expression cannot be predicted solely from profiling the structure and sequence of the genome. This highlights why it is important to interrogate the effect transposable elements have ona gene's role within a cell.

Transposable elements are largely disregarded in genomics due to technical difficulties in analysing these repetitive stretches of DNA. But characteristic variations within a population may in part be driven by differences in these parts of the genome, which may also be implicated in diseases such as cancer. Identifying which transposable elements are important for driving gene expression, and linking their actions to specific traits could aid the discovery of important genetic variants.