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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Noor, Nudrat 
Bitoun, Emmanuelle 
Tumian, Afidalina 

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.

Description

Keywords

KRAB, PRDM9, chromosomes, evolutionary biology, genes, genomics, human, meiosis, recombination, transposable elements, zinc finger protein, Binding Sites, Chromosome Mapping, DNA, HEK293 Cells, Histone-Lysine N-Methyltransferase, Homologous Recombination, Humans, Meiosis, Protein Binding, Protein Multimerization

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

6

Publisher

eLife Sciences Publications, Ltd