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

• Main Authors: Altemose, Nicolas, Noor, Nudrat, Bitoun, Emmanuelle, Tumian, Afidalina, Imbeault, Michaël, Chapman, J. Ross, Aricescu, A. Radu, Myers, Simon R.
• Format: Article
• Language: English; English
• Published: eLife Sciences Publications 2017
• Subjects: QH301 Biology; QH426 Genetics
• Online Access: http://irep.iium.edu.my/59029/13/59029-A%20map%20of%20human%20PRDM9%20binding.pdf; http://irep.iium.edu.my/59029/7/59029-A%20map%20of%20human%20PRDM9%20binding_scopus.pdf; http://irep.iium.edu.my/59029/; https://elifesciences.org/articles/28383
• Institution: Universiti Islam Antarabangsa Malaysia

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.