Convergent genes shape budding yeast pericentromeres
Convergent genes shape budding yeast pericentromeres
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DOI：
10.1038/s41586-020-2244-6
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发表时间：
2019-03
期刊：
影响因子：
64.8
通讯作者：
F. Paldi;Bonnie M. Alver;Daniel Robertson;S. Schalbetter;Alastair R W Kerr;D. Kelly;Matthew J. Neale;J. Baxter;A. Marston
中科院分区：
文献类型：
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作者：
F. Paldi;Bonnie M. Alver;Daniel Robertson;S. Schalbetter;Alastair R W Kerr;D. Kelly;Matthew J. Neale;J. Baxter;A. Marston
基因组的三维结构控制着它的维持、表达和传递。粘着蛋白复合物通过拓扑连接远距离基因座来组织基因组，并且高度富集在着丝粒周围的专门染色体结构域中，称为近着丝粒，-。本文报道了芽殖酵母（Saccharomycescerevisiae）近着丝粒的三维结构，并建立了基因组组织与功能之间的关系。我们发现，收敛基因标记的pericentromere边界，并与核心着丝粒，定义其结构和功能定位粘着蛋白。着丝粒装载粘着蛋白，着丝粒周围边缘的会聚基因将其捕获。着丝粒周围的每一侧组织成环状构象，边缘会聚基因位于基部。微管附着延伸一个单一的着丝粒周围环，其大小受其边界处会聚基因的限制。在有丝分裂过程中，将边缘基因重定向为串联构型，重新定位粘着蛋白，扩大着丝粒周围，并损害染色体双定向。因此，转录单位的线性排列与靶向粘附素加载一起将近着丝粒形成为能够进行染色体分离的结构。我们的研究结果揭示了着丝粒嵌入的染色体区域的结构，以及微管附着引起的重组。此外，我们建立了一个直接的，因果关系之间的三维基因组组织的特定染色体结构域和细胞功能。
The three-dimensional architecture of the genome governs its maintenance, expression and transmission. The cohesin protein complex organizes the genome by topologically linking distant loci, and is highly enriched in specialized chromosomal domains surrounding centromeres, called pericentromeres, , , , –. Here we report the three-dimensional structure of pericentromeres in budding yeast (Saccharomyces cerevisiae) and establish the relationship between genome organization and function. We find that convergent genes mark pericentromere borders and, together with core centromeres, define their structure and function by positioning cohesin. Centromeres load cohesin, and convergent genes at pericentromere borders trap it. Each side of the pericentromere is organized into a looped conformation, with border convergent genes at the base. Microtubule attachment extends a single pericentromere loop, size-limited by convergent genes at its borders. Reorienting genes at borders into a tandem configuration repositions cohesin, enlarges the pericentromere and impairs chromosome biorientation during mitosis. Thus, the linear arrangement of transcriptional units together with targeted cohesin loading shapes pericentromeres into a structure that is competent for chromosome segregation. Our results reveal the architecture of the chromosomal region within which kinetochores are embedded, as well as the restructuring caused by microtubule attachment. Furthermore, we establish a direct, causal relationship between the three-dimensional genome organization of a specific chromosomal domain and cellular function.