In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
- Corinne Grey1,6,
- Julie A.J. Clément1,6,
- Jérôme Buard1,
- Benjamin Leblanc2,
- Ivo Gut3,4,
- Marta Gut3,4,
- Laurent Duret5 and
- Bernard de Massy1
- 1Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 34396 Montpellier Cedex 05, France;
- 2Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark;
- 3CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain;
- 4Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain;
- 5Université de Lyon, Université Claude Bernard, CNRS, Laboratoire de Biométrie et Biologie Evolutive UMR 5558, F-69100, Villeurbanne, France
- Corresponding authors: corinne.grey{at}igh.cnrs.fr; bernard.de-massy{at}igh.cnrs.fr
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↵6 These authors are co-first authors and contributed equally to this work.
Abstract
In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner. Another subset reveals DSB-independent interactions between PRDM9 and genomic sites, such as the binding sites for the insulator protein CTCF. We propose that these DSB-independent sites result from interactions between hotspot-bound PRDM9 and genomic sequences located on the chromosome axis.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.217240.116.
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Freely available online through the Genome Research Open Access option.
- Received October 18, 2016.
- Accepted February 23, 2017.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
