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Identification of a BET family bromodomain/casein kinase II/TAF-containing complex as a regulator of mitotic condensin function

Kim HS 1 , Mukhopadhyay R 1 , Rothbart SB 2 , Silva AC 1 , Vanoosthuyse V 3 , Radovani E 4 Show all authors , Kislinger T 5 , Roguev A 6 , Ryan CJ 7 , Xu J 6 , Jahari H 8 , Hardwick KG 3 , Greenblatt JF 9 , Krogan NJ 10 , Fillingham JS 4 , Strahl BD 2 , Bouhassira EE 1 , Edelmann W 1 , Keogh MC 11

Affiliations 

  • 1 Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA
  • 2 Department of Biochemistry and Biophysics, UNC School of Medicine, Chapel Hill, NC 27599, USA
  • 3 Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3QR, Scotland
  • 4 Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada
  • 5 Princess Margaret Cancer Center, Toronto, ON M5G 1L7, Canada
  • 6 Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA
  • 7 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
  • 8 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
  • 9 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada
  • 10 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
  • 11 Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA. Electronic address: michael.keogh@einstein.yu.edu
Cell Rep, 2014 Mar 13;6(5):892-905.
PMID: 24565511 DOI: 10.1016/j.celrep.2014.01.029

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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