Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function

Hyun-Soo Kim; Rituparna Mukhopadhyay; Scott B Rothbart; Andrea C Silva; Vincent Vanoosthuyse; Ernest Radovani; Thomas Kislinger; Assen Roguev; Colm J Ryan; Jiewei Xu; Harlizawati Jahari; Kevin G Hardwick; Jack F Greenblatt; Nevan J Krogan; Jeffrey S Fillingham; Brian D Strahl; Eric E Bouhassira; Winfried Edelmann; Michael-Christopher Keogh

doi:10.1016/j.celrep.2014.01.029

Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function

Hyun-Soo Kim, Rituparna Mukhopadhyay, Scott B Rothbart, Andrea C Silva, Vincent Vanoosthuyse, Ernest Radovani, Thomas Kislinger, Assen Roguev, Colm J Ryan, Jiewei Xu, Harlizawati Jahari, Kevin G Hardwick, Jack F Greenblatt, Nevan J Krogan, Jeffrey S Fillingham, Brian D Strahl, Eric E Bouhassira, Winfried Edelmann, Michael-Christopher Keogh

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	892-905
Number of pages	14
Journal	Cell Reports
Volume	6
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2014.01.029
Publication status	Published - 13 Mar 2014

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10.1016/j.celrep.2014.01.029

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Kim, H.-S., Mukhopadhyay, R., Rothbart, S. B., Silva, A. C., Vanoosthuyse, V., Radovani, E., Kislinger, T., Roguev, A., Ryan, C. J., Xu, J., Jahari, H., Hardwick, K. G., Greenblatt, J. F., Krogan, N. J., Fillingham, J. S., Strahl, B. D., Bouhassira, E. E., Edelmann, W., & Keogh, M.-C. (2014). Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function. Cell Reports, 6(5), 892-905. https://doi.org/10.1016/j.celrep.2014.01.029

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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.",

author = "Hyun-Soo Kim and Rituparna Mukhopadhyay and Rothbart, {Scott B} and Silva, {Andrea C} and Vincent Vanoosthuyse and Ernest Radovani and Thomas Kislinger and Assen Roguev and Ryan, {Colm J} and Jiewei Xu and Harlizawati Jahari and Hardwick, {Kevin G} and Greenblatt, {Jack F} and Krogan, {Nevan J} and Fillingham, {Jeffrey S} and Strahl, {Brian D} and Bouhassira, {Eric E} and Winfried Edelmann and Michael-Christopher Keogh",

year = "2014",

month = mar,

day = "13",

doi = "10.1016/j.celrep.2014.01.029",

language = "English",

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Kim, H-S, Mukhopadhyay, R, Rothbart, SB, Silva, AC, Vanoosthuyse, V, Radovani, E, Kislinger, T, Roguev, A, Ryan, CJ, Xu, J, Jahari, H, Hardwick, KG, Greenblatt, JF, Krogan, NJ, Fillingham, JS, Strahl, BD, Bouhassira, EE, Edelmann, W & Keogh, M-C 2014, 'Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function', Cell Reports, vol. 6, no. 5, pp. 892-905. https://doi.org/10.1016/j.celrep.2014.01.029

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

PY - 2014/3/13

Y1 - 2014/3/13

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 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.

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 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.

U2 - 10.1016/j.celrep.2014.01.029

DO - 10.1016/j.celrep.2014.01.029

M3 - Article

C2 - 24565511

SN - 2211-1247

VL - 6

SP - 892

EP - 905

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -

Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function

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