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Transposable elements, including remnants of viral DNA retained in the genome for millions of years, make up a substantial fraction of mammalian genomes, and their effects on gene expression are thought to have driven speciation.
However, while there is anecdotal and circumstantial evidence suggesting these elements affect gene regulation—such as transcription factor binding sites in their sequences—techniques for systematically analyzing these elements’ activities are limited, says Joanna Wysocka of Stanford University School of Medicine. (See “Can Viruses in the Genome Cause Disease? The Threat of Ancient Viruses Tucked in the Human Genome.”) “So we don’t know overall how important they may be.”
Using a single short RNA, such as a CRISPR guide RNA, to manipulate transcriptional activity at multiple copies of an element should work in theory, says Wysocka. But in practice, “because over evolutionary time [the elements] accumulate mutations, they are different enough that . ...