Mer2 ChIP-seq

To segregate accurately during meiosis, homologous chromosomes in most species must recombine. Very small chromosomes would risk missegregation if recombination were randomly distributed, so the double-strand breaks (DSBs) that initiate recombination are not haphazard. How this nonrandomness is controlled is not understood. Here we demonstrate that Saccharomyces cerevisiae integrates multiple, temporally distinct pathways to regulate chromosomal binding of pro-DSB factors Rec114 and Mer2, thereby controlling duration of a DSB-competent state. Homologous chromosome engagement regulates Rec114/Mer2 dissociation late in prophase, whereas replication timing and proximity to centromeres or telomeres influence timing and amount of Rec114/Mer2 accumulation early. A distinct early mechanism boosts Rec114/Mer2 binding quickly to high levels specifically on the shortest chromosomes, dependent on chromosome axis proteins and subject to selection pressure to maintain hyperrecombinogenic properties of these chromosomes. Thus, an organism’s karyotype and its attendant risk of meiotic missegregation influence the shape and evolution of its recombination landscape.绝大多数物种的同源染色体需发生重组，方可在减数分裂过程中实现精准分离。若重组随机分布，极小染色体便会出现分离错误风险，因此启动重组的双链断裂（double-strand breaks, DSBs）并非随机发生。目前学界尚未明确这种非随机性的调控机制。本研究证实，酿酒酵母（Saccharomyces cerevisiae）通过整合多条时序迥异的通路，调控促DSB因子Rec114与Mer2的染色体结合，进而调控具备DSB形成能力的状态的持续时长。同源染色体结合可调控减数分裂前期晚期Rec114/Mer2的解离，而复制时序、与着丝粒或端粒的邻近程度则会影响减数分裂早期Rec114/Mer2的积累时序与积累量。存在一种独特的早期机制，可特异性地在最短染色体上快速将Rec114/Mer2的结合水平提升至高位，该机制依赖于染色体轴蛋白，并受到维持此类染色体高重组活性特性的选择压力调控。由此可见，生物体的核型及其伴随的减数分裂分离错误风险，会对其重组图谱的形态与演化产生影响。