title: Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis.
abstract: Phosphorylation of histone H3 threonine 118 (H3 T118ph) weakens histone DNA-contacts, disrupting the nucleosome structure. We show that Aurora-A mediated H3 T118ph occurs at pericentromeres and chromosome arms during prophase and is lost upon chromosome alignment. Expression of H3 T118E or H3 T118I (a SIN mutation that bypasses the need for the ATP-dependent nucleosome remodeler SWI/SNF) leads to mitotic problems including defects in spindle attachment, delayed cytokinesis, reduced chromatin packaging, cohesion loss, cohesin and condensin I loss in human cells. In agreement, overexpression of Aurora-A leads to increased H3 T118ph levels, causing cohesion loss, and reduced levels of cohesin and condensin I on chromatin. Normal levels of H3 T118ph are important because it is required for development in fruit flies. We propose that H3 T118ph alters the chromatin structure during specific phases of mitosis to promote timely condensin I and cohesin disassociation, which is essential for effective chromosome segregation.
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Candice L
authors.initials: CL
authors.lastname: Wike
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Hillary K
authors.initials: HK
authors.lastname: Graves
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Reva
authors.initials: R
authors.lastname: Hawkins
authors.affiliation: Department of Physics, The Ohio State University, Columbus, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Gibson
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, United States.
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Ferdinand
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
authors.forename: Damien F
authors.initials: DF
authors.lastname: Hudson
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, United States.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Ottesen
authors.affiliation: Department of Physics, The Ohio State University, Columbus, United States.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
authors.affiliation: Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Jill
authors.initials: J
authors.lastname: Schumacher
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States.
authors.forename: Jessica K
authors.identifier: http://orcid.org/0000-0001-9765-1659
authors.initials: JK
authors.lastname: Tyler
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013912:Threonine / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D013912:Threonine; D000097722:Cohesins; C108312:condensin complexes; C576917:AURKA protein, human
keywords: <i>c. elegans</i>; <i>d. melanogaster</i>; aurora-A; chromosome congression; chromosomes; cohesion; condensin; genes; histone H3 phosphorylation; human