Cohesin residency determines chromatin loop patterns

The organization of chromatin into higher-order structures is essential for chromosome segregation, the repair of DNA damage, and the regulation of gene expression. These structures are formed by the evolutionarily conserved SMC (structural maintenance of chromosomes) complexes. By analyzing synchronized populations of budding yeast with Micro-C, we observed that chromatin loops are formed genome-wide, and are dependent upon the SMC complex, cohesin. We correlated the loop signal with the position and intensity of cohesin binding to chromosomes in wild-type and cells depleted for the cohesin regulators Wpl1p and Pds5p. We generate a model to explain how the genomic distribution and frequency of loops are driven by cohesin residency on chromosomes. In this model a dynamic pool of cohesin with loop extrusion activity stops when encounters two regions occupied by stably bound cohesin, forming a loop. Different regions are occupied by cohesin in different cells, defining different patterns of chromatin loops.染色质组装为高级结构，对于染色体分离、DNA损伤修复以及基因表达调控均至关重要。这类高级结构由进化保守的SMC（structural maintenance of chromosomes，染色体结构维持）复合物组装形成。我们通过Micro-C技术分析同步化的出芽酵母群体，发现全基因组范围内均存在染色质环，且该结构依赖于SMC复合物黏连蛋白（cohesin）。我们将染色质环的信号特征，与野生型细胞以及黏连蛋白调控因子Wpl1p、Pds5p耗尽的细胞中，黏连蛋白在染色体上的结合位置与结合强度进行了关联分析。我们构建了一个模型，用以阐释染色质环的基因组分布与形成频率如何由黏连蛋白在染色体上的驻留过程所驱动。在该模型中，具备环挤出活性的动态黏连蛋白池，在遇到两处被稳定结合的黏连蛋白占据的染色体区域时会停止运动，进而形成染色质环。不同细胞中黏连蛋白所占据的染色体区域存在差异，由此定义了各异的染色质环模式。