Human PRDM9 Can Bind And Activate Promoters, And Other Zinc-Finger Proteins Associate With Reduced Recombination In cis

Abstract

Across mammals, PRDM9 binding localizes almost all meiotic recombination hotspots. However, most PRDM9 motif sequence matches are not bound, and most PRDM9-bound loci do not become hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human and chimp PRDM9 binding sites in a human cell line, and measured PRDM9-induced H3K4me3 and gene expression changes. These data revealed varied DNA-binding modalities of PRDM9, and histone modifications that predict binding. At sites where PRDM9 binds, specific cis sequence motifs associated with TRIM28 recruitment, and histone modifications, predict whether recombination subsequently occurs. These results implicate the large family of KRAB-ZNF genes in consistent, localized meiotic recombination suppression. PRDM9 affects gene expression for a small number of genes including CTCFL and VCX, by binding nearby. Finally, we show that PRDM9's DNA-binding zinc finger domain strongly impacts the formation of multimers, with a pair of highly diverged alleles multimerizing less efficiently.