Genome-wide variability in recombination activity is associated with meiotic chromatin organization

Abstract

BackgroundRecombination enables reciprocal exchange of genomic information between parental chromosomes and successful segregation of homologous chromosomes during meiosis. Errors in this process lead to negative health outcomes, while variability in recombination rate affects genome evolution. In mammals, most crossovers occur in hotspots defined by PRDM9 motifs, though PRDM9 binding sites are not all equally hot. We hypothesize that dynamic patterns of meiotic genome folding are linked to recombination activity. ResultsWe apply an integrative bioinformatics approach to analyze how three-dimensional (3D) chromosomal organization during meiosis relates to rates of double-strandbreak (DSB) and crossover formation at PRDM9 hotspots. We show that active, spatially accessible genomic regions during meiotic prophase are associated with DSB-favoured hotspots, which further adopt a transient locally active configuration in early prophase. Conversely, crossover formation is depleted among DSBs in spatially accessible regions during meiotic prophase, particularly within gene bodies. We also find evidence that active chromatin regions have smaller average loop sizes in mammalian meiosis. Collectively, these findings establish that differences in chromatin architecture along chromosomal axes are associated with variable recombination activity. ConclusionsWe propose an updated framework describing how 3D organization of brush-loop chromosomes during meiosis may modulate recombination.