title: Mitotic Transcription Installs Sgo1 at Centromeres to Coordinate Chromosome Segregation.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Warrington
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
authors.forename: Allyson
authors.initials: A
authors.lastname: Rice
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
authors.forename: Ningyan
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA. Electronic address: hongtao.yu@utsouthwestern.edu.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II; D000097722:Cohesins; C496644:SGO1 protein, human; C584277:BUB1 protein, human