In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites.
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.
Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 34396 Montpellier Cedex 05, France.
Corinne
C
Grey
Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 34396 Montpellier Cedex 05, France.
Julie A J
JA
Clément
Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 34396 Montpellier Cedex 05, France.
Jérôme
J
Buard
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.
Benjamin
B
Leblanc
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Ivo
I
Gut
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Marta
M
Gut
Université de Lyon, Université Claude Bernard, CNRS, Laboratoire de Biométrie et Biologie Evolutive UMR 5558, F-69100, Villeurbanne, France.
Laurent
L
Duret
Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 34396 Montpellier Cedex 05, France.
Bernard
0000-0002-0950-2758
B
de Massy
D000818:Animals; D000076246:CCCTC-Binding Factor / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D016678:Genome; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013090:Spermatocytes / Q000378:metabolism
D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D011495:Histone-Lysine N-Methyltransferase; C534829:prdm9 protein, mouse