有丝分裂转录将 Sgo1 安装在着丝粒处以协调染色体分离。

Mitotic Transcription Installs Sgo1 at Centromeres to Coordinate Chromosome Segregation.

机构信息

Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.

出版信息

Mol Cell. 2015 Aug 6;59(3):426-36. doi: 10.1016/j.molcel.2015.06.018. Epub 2015 Jul 16.

DOI:10.1016/j.molcel.2015.06.018

PMID:26190260

Abstract

Human sister chromatids at metaphase are primarily linked by centromeric cohesion, forming the iconic X shape. Premature loss of centromeric cohesion disrupts orderly mitotic progression. Shugoshin (Sgo1) binds to and protects cohesin at inner centromeres. The kinetochore kinase Bub1 phosphorylates histone H2A at T120 (H2A-pT120) and recruits Sgo1 to kinetochores, 0.5 μm from inner centromeres. Here, we show that Sgo1 is a direct reader of the H2A-pT120 mark. Bub1 also recruits RNA polymerase II (Pol II) to unattached kinetochores and promotes active transcription at mitotic kinetochores. Mitosis-specific inactivation of Pol II traps Sgo1 at kinetochores and weakens centromeric cohesion. Sgo1 interacts with Pol II in human cells and with RNA in vitro. We propose that Pol II-dependent transcription enables kinetochore-bound Sgo1 initially recruited by H2A-pT120 to reach cohesin embedded in centromeric chromatin. Our study implicates mitotic transcription in targeting regulatory factors to highly compacted mitotic chromatin.

摘要

人类中期姐妹染色单体主要通过着丝粒黏合相连，形成标志性的 X 形。着丝粒黏合过早丢失会破坏有丝分裂的有序进行。Shugoshin（Sgo1）与着丝粒内部的黏合蛋白结合并对其起到保护作用。动粒激酶 Bub1 将组蛋白 H2A 的第 120 位苏氨酸磷酸化（H2A-pT120），并招募 Sgo1 到距离着丝粒内部 0.5μm 的动粒上。在这里，我们证明 Sgo1 是 H2A-pT120 标记的直接读取器。Bub1 还招募 RNA 聚合酶 II（Pol II）到未连接的动粒上，并在有丝分裂动粒上促进活跃的转录。Pol II 在有丝分裂特异性失活时会将 Sgo1 捕获在动粒上，并削弱着丝粒黏合。Sgo1 在人类细胞中与 Pol II 相互作用，并在体外与 RNA 相互作用。我们提出，Pol II 依赖性转录使最初由 H2A-pT120 招募的动粒结合 Sgo1 能够到达位于着丝粒染色质内的黏合蛋白。我们的研究表明，有丝分裂转录将调节因子靶向高度浓缩的有丝分裂染色质。