Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

Retrotransposons, also known as jumping genes, have invaded the genomes of most living organisms. These fragments of DNA have the ability to move or copy themselves from one location of a chromosome to another. Depending on where they insert themselves, retrotransposonscan modify the sequence of nearby genes, which can alter or even abolish their activity. Although these genetic modifications have contributed significantly to the evolution of different species, retrotransposonscan also have detrimental effects; for example, by causing new cases of genetic diseases. Adult human cells have a number of mechanisms that work to keep the activity of retrotransposonsat a very low level. However, in many types of cancers retrotransposonsescape these defense mechanisms and ‘jump’ actively. This is thought to contribute to the development and spread of cancerous tumors. To understand how jumping genesare mobilized, a fundamental question must be answered: is the high jumping geneactivity observed in some cell types a result of activating many copies of the retrotransposons, or only a few of them? This question has been difficult to address because there are more than one hundred copies of retrotransposonsthat could potentially move in humans, many of which have not even been referenced in the human genome map. Furthermore, each copy is almost identical to another one, making it difficult to discriminate between them. Philippe et al. have now developed an approach that can map where individual retrotransposonsare located in the genome of normal and cancerous cells and measure how active these jumping genesare. This revealed that only a very restricted number of them are active in any given cell type. Moreover, different subsets of jumping genesare active in different cell types, and their locations in the genome often do not overlap. Thus, whether jumping genesare activated depends on the cell type and their position in the genome. These results are in contrast to the prevalent view that retrotransposonsare activated in a more widespread manner across the genome, at least in cancerous cells. Overall, Philippe et al.’s findings pave the way towards characterizing the chromosome regions in which retrotransposonsare frequently activated and understanding how they contribute to cancer and other diseases.