Arabidopsis meiotic crossover hot spots overlap with H2A.Z nucleosomes at gene promoters

Abstract

PRDM9 directs human meiotic crossover hotspots to intergenic sequence motifs, whereas budding yeast hotspots overlap low nucleosome density regions in gene promoters. To investigate hotspots in plants, which lack PRDM9, we used coalescent analysis of Arabidopsis genetic variation. Crossovers increase towards gene promoters and terminators, and hotspots are associated with active chromatin modifications, including H2A.Z, histone H3K4me3, low nucleosome density and low DNA methylation. Hotspot-enriched A-rich and CTT-repeat DNA motifs occur upstream and downstream of transcriptional start respectively. Crossovers are asymmetric around promoters and highest over CTT-motifs and H2A.Z-nucleosomes. Pollen-typing, segregation and cytogenetic analysis show decreased crossovers in the arp6 H2A.Z deposition mutant, at multiple scales. During meiosis H2A.Z and DMC1/RAD51 recombinases form overlapping chromosomal foci. As arp6 reduces DMC1/RAD51 foci, H2A.Z may promote formation or processing of meiotic DNA double-strand breaks. We propose that gene chromatin ancestrally designates hotspots within eukaryotes and PRDM9 is a derived state within vertebrates.

High-Resolution Mapping of Crossover Events in the Hexaploid Wheat Genome Suggests a Universal Recombination Mechanism

“…In Mimulus, a collection of 98 individuals was used to precisely locate 414,734 CO-or geneconversion events, among which 3235 were highly reliable recombination hotspots and 13,000 were considered bona fide COs. In Arabidopsis, megabase-scale variations in CO frequencies along the chromosomes, with an increase from telomere to centromere, were observed (Choi et al 2013;Drouaud et al 2013). Two previously identified hotspots (3a and 3b; Yelina et al 2012) were confirmed by allelespecific amplification from gamete DNA (pollen typing; Drouaud and Mézard 2011).…”

“…Two previously identified hotspots (3a and 3b; Yelina et al 2012) were confirmed by allelespecific amplification from gamete DNA (pollen typing; Drouaud and Mézard 2011). In both cases (Mimulus and Arabidopsis), CO frequency increases toward transcriptional start sites (TSSs)-and to a lower extent toward transcriptional termination sites (TTSs) in Arabidopsis (Choi et al 2013)-and fall off sharply just after, thus exhibiting polarity. In sorghum, a similar correlation was observed with 97-98% of COs occurring in euchromatin regions (Paterson et al 2009).…”

“…In plants, no homolog to PRDM9 subfamily was found (Zhang and Ma 2012). However, most H3K4me3-methylase encoding genes are expressed in meiotic cells in Arabidopsis and rice (Zhang and Ma 2012), and this mark is associated with recombinogenic regions in Arabidopsis and barley (Choi et al 2013;Aliyeva-Schnorr et al 2015;Shilo et al 2015). This may even be a general eukaryotic regulatory mechanism and may have originated in the ancestor of eukaryotes (Zhang and Ma 2012;Mercier et al 2015).…”

“…For cultivated crops, this implies a decrease of the breeding power in regions showing low CO rates (Rodgers-Melnick et al 2015). In human, Saccharomyces cerevisiae, Arabidopsis, and wheat, .80% of the recombination events occur in less than a quarter of the genome (Myers et al 2005;Chen et al 2008;Mancera et al 2008;Choi et al 2013;International Wheat Genome Sequencing Consortium 2014). This nonhomogeneity of CO distribution is the basis of the definition of recombination hotspots and coldspots (which have significantly high and low CO frequencies, respectively).…”

“…In plants, coalescent theory was successfully applied to generate maps of CO frequency and hotspots in monkey flower (Mimulus guttatus; Hellsten et al 2013) and in Arabidopsis thaliana, (Choi et al 2013). In Mimulus, a collection of 98 individuals was used to precisely locate 414,734 CO-or geneconversion events, among which 3235 were highly reliable recombination hotspots and 13,000 were considered bona fide COs.…”