A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

Elife. 2017 Oct 26;6:e28383. doi: 10.7554/eLife.28383.

Abstract

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.

Keywords: KRAB; PRDM9; chromosomes; evolutionary biology; genes; genomics; human; meiosis; recombination; transposable elements; zinc finger protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chromosome Mapping
  • DNA / metabolism*
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Homologous Recombination*
  • Humans
  • Meiosis*
  • Protein Binding
  • Protein Multimerization

Substances

  • DNA
  • Histone-Lysine N-Methyltransferase
  • PRDM9 protein, human