Transcription promotes discrete long-range chromatin loops and 3D domains besides organizing cohesin-mediated folding

The multi-layered arrangement of eukaryotic genomes and chromosome spatial organization dynamics are of functional importance for gene expression, DNA replication and segregation. Cohesin is an essential instrument of chromosome folding by carrying out long range intra-chromatid DNA looping in addition to allowing timely chromosome segregation. Cohesin also ensures dynamic regulation of gene expression in mammals by promoting interaction between distal regulatory elements and promoters whereas transcription affects genome folding in multiple ways in multiple organisms. Here, we comprehensively dissect the relative contributions of transcription and cohesin complexes as well as their interplay on the yeast S.cerevisiae genome organization through DNA borders and loops. Transcription activation specifically induces apparition of DNA borders and loops, independently of cohesin, interfering in addition with cohesin mediated loop expansion.真核生物基因组的多层级排布与染色体空间组织动态，对于基因表达、DNA复制及染色体分离均具有重要的功能意义。黏连蛋白（Cohesin）是染色体折叠的核心工具，其可介导染色单体内部远距离DNA环的形成，同时保障染色体适时分离。此外，黏连蛋白还可通过促进远端调控元件与启动子之间的相互作用，实现哺乳动物体内基因表达的动态调控；而转录过程则在多种生物中以多种方式影响基因组折叠。本研究通过DNA边界与DNA环，全面解析了转录与黏连蛋白复合物各自的相对贡献，以及二者之间的相互作用对酿酒酵母（S.cerevisiae）基因组组织的影响。转录激活可特异性诱导DNA边界与DNA环的形成，且该过程不依赖于黏连蛋白，同时还会干扰黏连蛋白介导的环扩张过程。