A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis
- University of Oxford, United Kingdom
- École Polytechnique Fédérale de Lausanne, Switzerland
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.
Data availability
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Mapping PRDM9 binding and its effects in transfected HEK293T cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE99407).
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Recombination initiation maps of individual human genomesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE59836).
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ChIP-exo of human KRAB-ZNFs transduced in HEK 293T cells and KAP1 in hES H1 cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE78099).
Article and author information
Author details
Funding
Wellcome (Investigator Award 098387/Z/12/Z)
- Simon R Myers
Cancer Research UK (Career Development Fellowship C52690/A19270)
- J Ross Chapman
Howard Hughes Medical Institute (Gilliam Fellowship for Advanced Study)
- Nicolas Altemose
Medical Research Council (Grant MR/L009609/1)
- A Radu Aricescu
Foreign and Commonwealth Office (Marshall Scholarship)
- Nicolas Altemose
Wellcome (Core Award 090532/Z/09/Z)
- Nicolas Altemose
- Nudrat Noor
- Emmanuelle Bitoun
- J Ross Chapman
- A Radu Aricescu
- Simon R Myers
Wellcome (DPhil Studentship 086817/Z/08/Z)
- Nudrat Noor
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Altemose et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis
eLife 6:e28383.
https://doi.org/10.7554/eLife.28383
