TY - JOUR
T1 - Identification of a BET family bromodomain/casein kinase II/TAF-containing complex as a regulator of mitotic condensin function
AU - Kim, Hyun Soo
AU - Mukhopadhyay, Rituparna
AU - Rothbart, Scott B.
AU - Silva, Andrea C.
AU - Vanoosthuyse, Vincent
AU - Radovani, Ernest
AU - Kislinger, Thomas
AU - Roguev, Assen
AU - Ryan, Colm J.
AU - Xu, Jiewei
AU - Jahari, Harlizawati
AU - Hardwick, Kevin G.
AU - Greenblatt, Jack F.
AU - Krogan, Nevan J.
AU - Fillingham, Jeffrey S.
AU - Strahl, Brian D.
AU - Bouhassira, Eric E.
AU - Edelmann, Winfried
AU - Keogh, Michael Christopher
N1 - Funding Information:
We thank Steve Buratowski, Julien Lajugie, Andrew McLellan, Jamie Moseley, Charles Query, Mike Shales, Arthur Skoultchi, Jon Warner, and Ian Willis for help and advice and Robin Allshire, Mark Bedford, James Bradner, Dan Finley, Keith Gull, Tetsuro Kokubo, and Richard Maraia for the generous supply of materials. C.J.R. was supported by ICON plc and the UCD Newman Fellowship Program. J.S.F. was supported by start-up funding from Ryerson University and a discovery grant from the Natural Sciences and Engineering Research Council of Canada. T.K. is a Canada Research Chair in Proteomics of Cancer Research. This work was also supported in part by the National Institutes of Health (ES019966, GM085394 and GM068088); the Canadian Institutes of Health Research (MT-6092); NYSTEM, the funding agency of the Empire State Stem Cell Board (C024405 and C024172); pilot funding from the AECOM Epigenomics facility; and an NCI Cancer Center Support grant to Albert Einstein College of Medicine (CA013330).
PY - 2014
Y1 - 2014
N2 - 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 genomicregions 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 thefirst Nrc1 bromodomain. Strikingly, mutants inNCT 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 inorder to modulate the activity of condensin duringchromosome condensation and decondensation.
AB - 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 genomicregions 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 thefirst Nrc1 bromodomain. Strikingly, mutants inNCT 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 inorder to modulate the activity of condensin duringchromosome condensation and decondensation.
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U2 - 10.1016/j.celrep.2014.01.029
DO - 10.1016/j.celrep.2014.01.029
M3 - Article
C2 - 24565511
AN - SCOPUS:84895919564
SN - 2211-1247
VL - 6
SP - 892
EP - 905
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -