Zinc finger protein evolution against transposons and its impact on mammals

The Krüppel-associated box zinc finger protein (KRAB-ZFP) family rapidly amplified in response to invading transposable elements but their function in organismal development has gone largely unexplored. We determined the genomic binding sites of 61 murine KRAB-ZFPs and genetically deleted five large KRAB-ZFP gene clusters encoding nearly one third of mouse KRAB-ZFPs. We demonstrate that recently evolved mouse KRAB-ZFPs silence specific retrotransposon groups in the early embryo and block retrotransposon-borne enhancers from gene activation. KRAB-ZFP cluster KO mice display no overt phenotypes but display increased rates of somatic retrotransposition, indicating that KRAB-ZFPs limit the mobilization of retrotransposons in vivo.  Our data supports an arms-race model in which many KRAB-ZFPs evolve to repress retrotransposons from amplifying within the genome, minimizing the risk of insertional mutagenesis.