TY - JOUR T1 - Genome-wide variability in recombination activity is associated with meiotic chromatin organization JF - bioRxiv DO - 10.1101/2021.01.06.425599 SP - 2021.01.06.425599 AU - Xiaofan Jin AU - Geoff Fudenberg AU - Katherine S. Pollard Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/07/2021.01.06.425599.abstract N2 - Background Recombination 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.Results We 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.Conclusions We propose an updated framework describing how 3D organization of brush-loop chromosomes during meiosis may modulate recombination.Competing Interest StatementThe authors have declared no competing interest. ER -