| First Author | Wolf G | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32479262 | Mgi Jnum | J:291191 |
| Mgi Id | MGI:6442951 | Doi | 10.7554/eLife.56337 |
| Citation | Wolf G, et al. (2020) KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage. Elife 9:e56337 |
| abstractText | The Kruppel-associated box zinc finger protein (KRAB-ZFP) family diversified in mammals. The majority of human KRAB-ZFPs bind transposable elements (TEs), however, since most TEs are inactive in humans it is unclear whether KRAB-ZFPs emerged to suppress TEs. We demonstrate that many recently emerged murine KRAB-ZFPs also bind to TEs, including the active ETn, IAP, and L1 families. Using a CRISPR/Cas9-based engineering approach, we genetically deleted five large clusters of KRAB-ZFPs and demonstrate that target TEs are de-repressed, unleashing TE-encoded enhancers. Homozygous knockout mice lacking one of two KRAB-ZFP gene clusters on chromosome 2 and chromosome 4 were nonetheless viable. In pedigrees of chromosome 4 cluster KRAB-ZFP mutants, we identified numerous novel ETn insertions with a modest increase in mutants. Our data strongly support the current model that recent waves of retrotransposon activity drove the expansion of KRAB-ZFP genes in mice and that many KRAB-ZFPs play a redundant role restricting TE activity. |
