During meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative, and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization using Caenorhabditis elegans. Analyses of wild-type (WT) chromosomes and de novo circular minichromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with 2 functionally distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister-chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging 3 per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister-chromatid loops. Indeed, immunofluorescence fluorescence in situ hybridization (FISH) assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.

在减数分裂过程中，染色体采用专门的组织，涉及沿其长度组装基于粘着蛋白的轴，并从该轴发出DNA环。我们应用新的，定量的和广泛适用的细胞遗传学策略来阐明使用秀丽隐杆线虫的该组织的分子基础。对野生型（WT）染色体和新生圆形微染色体的分析显示，减数分裂特异的HORMA结构域蛋白以一定数量组装成队列，并将轴与2个功能不同的黏着蛋白复合物（REC-8和COH-3）共同组织在一起/ 4）的化学计量比。我们进一步发现，在S期加载并介导姐妹染色单体内聚的REC-8黏附素通常以单个复合物的形式出现，从而支持其中姐妹黏附由单个黏附素环局部介导的模型。REC-8复合物以交替的方式散布在有轴组织的COH-3 / 4复合物中（每组平均3个），这不足以赋予内聚力，但可以与单个染色单体结合，这提示一种机制可以形成不对称的姐妹染色单体循环。确实，免疫荧光荧光原位杂交（FISH）分析表明，在姐妹染色单体上形成的环之间的基因组含量之间存在频繁的不对称性。我们讨论从数据推断出的染色体轴/环结构特征如何帮助解释减数分裂程序的神秘但必不可少的方面。