Around half of our genetic content is composed of retrotransposons that are thought to be ancient viruses that have stably integrated into our genomes. These ancient viruses, as mobile genetic elements, have been drivers of evolution, creating new genes and plasticity of genomes, and many of them are species-specific.
Endogenous retroviruses are one type of retrotransposon family that resemble present day retroviruses like HIV, and as such, they are thought to have arisen from germ-line integrations of retroviruses. While these viruses that were once mobile are now mostly inactive through mutation, they have co-evolved with our genes to adopt normal functions in gene regulation. For example, exciting data including ours has shown that endogenous retroviruses retain regulatory sequences that can act as enhancers, repressors or alternative promoters for cellular genes in a temporal or tissue-specific way.
Very little is known about which transcription factors and complexes are recruited to retrotransposons though, except that several key transcription factors target repetitive sequences, like CTCF, OCT3/4 and LBP9, which has led to differences in the gene circuits controlled by these factors between species. We have set out to identify factors that target these ancient viruses in order to unravel how these pathways impact on normal gene regulation, genetic diseases and cancers.