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

Journal article

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.

Authors: Altemose, N; Noor, N; Bitoun, E; Tumian, A; Imbeault, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: eLife Sciences Publications
• Journal: eLife
• Volume: 6
• Article number: e28383
• Publication date: 2017-10-26
• Acceptance date: 2017-10-24
• DOI: 10.7554/elife.28383
• ISSN: 2050-084X
• Pmid: 29072575
• Language: English
• Keywords: genomics; evolutionary biology; genes; chromosomes; human