KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage

eLife

Didier Trono¹  Alberto de Iaco¹  Gernot Wolf²  Matthew Tinkham²  Sherry Ralls²  Don Hoang²  Apratim Mitra²  Todd S Macfarlan²  Ming-An Sun²  Melania Bruno² 

[1] School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;The Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, United States;

关键词: KRAB-ZFP;    transposable elements;    retrotransposons;    evolution;    chromatin;    development;   

DOI  :  10.7554/eLife.56337

来源: DOAJ

【 摘 要 】

The Krüppel-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.

【 授权许可】

Unknown