SRP308700 PRJNA705677 ZBTB43 eliminates Z-DNA in mouse prospermatogonia We present epigenomic evidence for the existence of a biological process that safeguards the mammalian genome by eliminating mutagenic Z-DNA structures in germ cells of the mouse male fetus. We show that a previously uncharacterized zinc finger protein, ZBTB43, binds to purine-pyrimidine repeats (PPRs) in the genome and by eliminating Z-DNA, promotes de novo DNA methylation at PPRs during a critical window of germline reprogramming.