Laboratory of virology and genetics LVG

Close to half of the human genome is derived from retroelements, amongst which endogenous retroviruses (ERVs) closely related to the human immunodeficiency virus. Although essential motors of evolution, these genetic invaders need to be tightly control, an action exerted through their transcriptional repression at the earliest embryonic stages. About 1’200 of the 20’000 genes contained in the human genome encode for transcriptional regulators, including some four hundred KRAB-containing zinc finger proteins (KRAB-ZFPs). KRAB-ZFPs are tetrapod-restricted, sequence-specific DNA binding transcriptional repressors, which act by triggering the formation of heterochromatin through their universal cofactor KAP1. KRAB-ZFP genes have been subjected to intense positive selection during evolution. At least partly explaining this phenomenon, we uncovered that KRAB-ZFPs and KAP1 are responsible for the early embryonic silencing of endogenous retroviruses, a class of rapidly evolving retrotransposons. This regulatory system thus probably first developed as an antiviral defense mechanism. Our ongoing work demonstrates that it has now been co-opted to function as a master regulator of mammalian homeostasis

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• Epigenetic control of retroelements
• Mechanistic studies of KRAB/KAP1-mediated regulation
• Our transgenesis facility