Genome-wide binding patterns of murine KRAB zinc finger proteins

Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. Here we report the identification of the genome-wide binding profiles of 61 mouse KRAB-ZFPs by overexpression of epitope-tagged transgenes. We found that 51 of these KRAB-ZFPs target at least one retrotransposon group. Interestingly, evolutionary young and still active retrotransposons such as IAP and ETn elements are targeted by several KRAB-ZFPs which are mainly encoded within two gene clusters that are not conserved in any other sequenced species. This indicated that an evolutionary arms race drives the rapid expansion of KRAB-ZFP genes in order to restrict active retrotransposons. Epitope tagged KRAB zinc finger proteins were overexpressed in F9 EC or B6 ES cells and ChIP-seq was performed to identify their genomic binding sites