RT Journal
A1 Baker, Christopher L.
A1 Walker, Michael
A1 Kajita, Shimpei
A1 Petkov, Petko M.
A1 Paigen, Kenneth
T1 PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration
JF Genome Research 
JO Genome Research 
YR 2014 
FD May 01 
VO 24 
IS 5 
SP 724 
OP 732 
DO 10.1101/gr.170167.113 
UL http://genome.cshlp.org/content/24/5/724.abstract 
AB In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Their locations are predominantly determined by the zinc finger protein PRDM9, which binds to DNA in hotspots and subsequently uses its SET domain to locally trimethylate histone H3 at lysine 4 (H3K4me3). This sets the stage for double-strand break (DSB) formation and reciprocal exchange of DNA between chromatids, forming Holliday junctions. Here we report genome-wide analyses of PRDM9-dependent histone modifications using two inbred mouse strains differing only in their PRDM9 zinc finger domain. We show that PRDM9 binding actively reorganizes nucleosomes into a symmetrical pattern, creating an extended nucleosome-depleted region. These regions are centered by a consensus PRDM9 binding motif, whose location and identity was confirmed in vitro. We also show that DSBs are centered over the PRDM9 binding motif within the nucleosome-depleted region. Combining these results with data from genetic crosses, we find that crossing-over is restricted to the region marked by H3K4me3. We suggest that PRDM9-modified nucleosomes create a permissible environment that first directs the location of DSBs and then defines the boundaries of Holliday junction branch migration.