title: Identification of a BET family bromodomain/casein kinase II/TAF-containing complex as a regulator of mitotic condensin function.
abstract: Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Biochemistry and Biophysics, UNC School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Rothbart
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Silva
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3QR, Scotland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vanoosthuyse
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Radovani
authors.affiliation: Princess Margaret Cancer Center, Toronto, ON M5G 1L7, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.affiliation: Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.affiliation: Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA; School of Medicine & Medical Science, University College, Dublin 4, Ireland.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA; Malaysian Institute of Pharmaceuticals and Nutraceuticals, 11800 USM Penang, Malaysia.
authors.forename: Harlizawati
authors.initials: H
authors.lastname: Jahari
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3QR, Scotland.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Hardwick
authors.affiliation: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
authors.affiliation: Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.affiliation: Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Fillingham
authors.affiliation: Department of Biochemistry and Biophysics, UNC School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA.
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA. Electronic address: michael.keogh@einstein.yu.edu.
authors.forename: Michael-Christopher
authors.initials: MC
authors.lastname: Keogh
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C108312:condensin complexes; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex; D047390:Casein Kinase II; D000251:Adenosine Triphosphatases