Deng Xiexiong, Kuo Min-Hao
Department of Biochemistry and Molecular Biology, Michigan State University. East Lansing, MI 48824.
Department of Biochemistry and Molecular Biology, Michigan State University. East Lansing, MI 48824
G3 (Bethesda). 2018 Aug 30;8(9):2901-2911. doi: 10.1534/g3.118.200522.
The spindle assembly checkpoint (SAC) is key to faithful segregation of chromosomes. One requirement that satisfies SAC is appropriate tension between sister chromatids at the metaphase-anaphase juncture. Proper tension generated by poleward pulling of mitotic spindles signals biorientation of the underlying chromosome. In the budding yeast, the tension status is monitored by the conserved Shugoshin protein, Sgo1p, and the tension sensing motif (TSM) of histone H3. ChIP-seq reveals a unique TSM-dependent, tripartite domain of Sgo1p in each mitotic chromosome. This domain consists of one centromeric and two flanking peaks 3 - 4 kb away, present exclusively in mitosis. Strikingly, this trident motif coincides with cohesin localization, but only at the centromere and the two immediate adjacent loci, despite that cohesin is enriched at numerous regions throughout mitotic chromosomes. Chromosome conformation capture assays reveal apparent looping at the centromeric and pericentric regions. The TSM-Sgo1p-cohesin triad is therefore at the center stage of higher-ordered chromatin architecture for error-free segregation.
纺锤体组装检查点（SAC）是染色体忠实分离的关键。满足SAC的一个条件是在中期 - 后期交界处姐妹染色单体之间有适当的张力。有丝分裂纺锤体向极方向牵拉产生的适当张力标志着基础染色体的双定向。在芽殖酵母中，张力状态由保守的守护蛋白Sgo1p和组蛋白H3的张力感应基序（TSM）监测。染色质免疫沉淀测序（ChIP-seq）揭示了在每个有丝分裂染色体中Sgo1p的一个独特的依赖TSM的三方结构域。该结构域由一个着丝粒峰和两个距离着丝粒3 - 4 kb的侧翼峰组成，仅在有丝分裂期出现。引人注目的是，这个三叉基序与黏连蛋白的定位重合，但仅在着丝粒和两个紧邻的位点，尽管黏连蛋白在整个有丝分裂染色体的许多区域都有富集。染色体构象捕获分析揭示了着丝粒和着丝粒周围区域明显的环化。因此，TSM - Sgo1p - 黏连蛋白三联体处于高阶染色质结构的中心阶段，以实现无误分离。
