Error message

No crossref credentials set for sci

Two Histone Marks Establish the Inner Centromere and Chromosome Bi-Orientation

Science, 8 October 2010
Vol. 330, Issue 6001, p. 239-243
DOI: 10.1126/science.1194498

Two Histone Marks Establish the Inner Centromere and Chromosome Bi-Orientation

  1. Yuya Yamagishi1,2,*,
  2. Takashi Honda1,3,*,
  3. Yuji Tanno1,
  4. Yoshinori Watanabe1,2,3,
  1. 1Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
  2. 2Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan.
  3. 3Graduate School of Agricultural and Life Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
  1. To whom correspondence should be addressed. E-mail: ywatanab{at}
  1. * These authors contributed equally to this work.


For proper partitioning of chromosomes in mitosis, the chromosomal passenger complex (CPC) including Aurora B and survivin must be localized at the center of paired kinetochores, at the site called the inner centromere. It is largely unknown what defines the inner centromere and how the CPC is targeted to this site. Here, we show that the phosphorylation of histone H3–threonine 3 (H3-pT3) mediated by Haspin cooperates with Bub1-mediated histone 2A–serine 121 (H2A-S121) phosphorylation in targeting the CPC to the inner centromere in fission yeast and human cells. H3-pT3 promotes nucleosome binding of survivin, whereas phosphorylated H2A-S121 facilitates the binding of shugoshin, the centromeric CPC adaptor. Haspin colocalizes with cohesin by associating with Pds5, whereas Bub1 localizes at kinetochores. Thus, the inner centromere is defined by intersection of two histone kinases.

  • Received for publication 30 June 2010.
  • Accepted for publication 17 August 2010.


Y. Yamagishi, T. Honda, Y. Tanno, and Y. Watanabe, Two Histone Marks Establish the Inner Centromere and Chromosome Bi-Orientation. Science 330, 239-243 (2010).

Kinetochore-localized BUB-1/BUB-3 complex promotes anaphase onset in C. elegans
T. Kim, M. W. Moyle, P. Lara-Gonzalez, C. De Groot, K. Oegema, and A. Desai
JCB 209, 507-517 (25 May 2015)

Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction
C. Reyes, C. Serrurier, T. Gauthier, Y. Gachet, and S. Tournier
JCB 208, 713-727 (16 March 2015)

Shugoshins: Tension-Sensitive Pericentromeric Adaptors Safeguarding Chromosome Segregation
A. L. Marston, C. Serrurier, T. Gauthier, Y. Gachet, and S. Tournier
Mol. Cell. Biol. 35, 634-648 (15 February 2015)

Molecular Pathways: Regulation and Targeting of Kinetochore-Microtubule Attachment in Cancer
J. A. Herman, C. M. Toledo, J. M. Olson, J. G. DeLuca, and P. J. Paddison
Clin. Cancer Res. 21, 233-239 (15 January 2015)

Loss of BRCA1 impairs centromeric cohesion and triggers chromosomal instability
A. Di Paolo, C. Racca, P. Calsou, and F. Larminat
FASEB J. 28, 5250-5261 (1 December 2014)

Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes
A. L. Nguyen, A. S. Gentilello, A. Z. Balboula, V. Shrivastava, J. Ohring, and K. Schindler
J. Cell Sci. 127, 5066-5078 (1 December 2014)

Inhibitor-3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore-bound protein phosphatase-1
A. Eiteneuer, J. Seiler, M. Weith, M. Beullens, B. Lesage, V. Krenn, A. Musacchio, M. Bollen, and H. Meyer
EMBO J. 33, 2704-2720 (18 November 2014)

Sgo1 recruits PP2A to chromosomes to ensure sister chromatid bi-orientation during mitosis
H. D. Eshleman, and D. O. Morgan
J. Cell Sci. 127, 4974-4983 (15 November 2014)

Regulation of Centromere Localization of the Drosophila Shugoshin MEI-S332 and Sister-Chromatid Cohesion in Meiosis
C. Nogueira, H. Kashevsky, B. Pinto, A. Clarke, and T. L. Orr-Weaver
G3 4, 1849-1858 (14 October 2014)

The Spatiotemporal Dynamics of Chromatin Protein HP1{alpha} Is Essential for Accurate Chromosome Segregation during Cell Division
L. Chu, Y. Huo, X. Liu, P. Yao, K. Thomas, H. Jiang, T. Zhu, G. Zhang, M. Chaudhry, G. Adams et al.
J Biol Chem 289, 26249-26262 (19 September 2014)

Chromatin Protein HP1{alpha} Interacts with the Mitotic Regulator Borealin Protein and Specifies the Centromere Localization of the Chromosomal Passenger Complex
X. Liu, Z. Song, Y. Huo, J. Zhang, T. Zhu, J. Wang, X. Zhao, F. Aikhionbare, J. Zhang, H. Duan et al.
J Biol Chem 289, 20638-20649 (25 July 2014)

Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase
A. Maiolica, M. de Medina-Redondo, E. M. Schoof, A. Chaikuad, F. Villa, M. Gatti, S. Jeganathan, H. J. Lou, K. Novy, S. Hauri et al.
MCP 13, 1724-1740 (1 July 2014)

Tension-dependent removal of pericentromeric shugoshin is an indicator of sister chromosome biorientation
O. O. Nerusheva, S. Galander, J. Fernius, D. Kelly, and A. L. Marston
Genes Dev. 28, 1291-1309 (15 June 2014)

EB1 enables spindle microtubules to regulate centromeric recruitment of Aurora B
B. Banerjee, C. A. Kestner, and P. T. Stukenberg
JCB 204, 947-963 (17 March 2014)

Polo-like kinase-1 triggers histone phosphorylation by Haspin in mitosis
L. Zhou, X. Tian, C. Zhu, F. Wang, and J. M. Higgins
EMBO Rep. 15, 273-281 (1 March 2014)

Kinetochore composition and its function: lessons from yeasts
Y. Yamagishi, T. Sakuno, Y. Goto, and Y. Watanabe
FEMS Microbiol Rev 38, 185-200 (1 March 2014)

A Cascade of Histone Modifications Induces Chromatin Condensation in Mitosis
B. J. Wilkins, N. A. Rall, Y. Ostwal, T. Kruitwagen, K. Hiragami-Hamada, M. Winkler, Y. Barral, W. Fischle, and H. Neumann
Science 343, 77-80 (3 January 2014)

KNL1 facilitates phosphorylation of outer kinetochore proteins by promoting Aurora B kinase activity
G. V. Caldas, K. F. DeLuca, and J. G. DeLuca
JCB 203, 957-969 (23 December 2013)

Arrayed BUB recruitment modules in the kinetochore scaffold KNL1 promote accurate chromosome segregation
M. Vleugel, E. Tromer, M. Omerzu, V. Groenewold, W. Nijenhuis, B. Snel, and G. J. P. L. Kops
JCB 203, 943-955 (23 December 2013)

Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres
M. Carretero, M. Ruiz-Torres, M. Rodriguez-Corsino, I. Barthelemy, and A. Losada
EMBO J. 32, 2938-2949 (13 November 2013)

Kinetochore Function and Chromosome Segregation Rely on Critical Residues in Histones H3 and H4 in Budding Yeast
T. M. Ng, T. L. Lenstra, N. Duggan, S. Jiang, S. Ceto, F. C. P. Holstege, J. Dai, J. D. Boeke, and S. Biggins
Genetics 195, 795-807 (1 November 2013)

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore
S. Biggins, T. L. Lenstra, N. Duggan, S. Jiang, S. Ceto, F. C. P. Holstege, J. Dai, J. D. Boeke, and S. Biggins
Genetics 194, 817-846 (1 August 2013)

The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly
T. Hori, W.-H. Shang, K. Takeuchi, and T. Fukagawa
JCB 200, 45-60 (7 January 2013)

Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes
A. Rattani, M. Wolna, M. Ploquin, W. Helmhart, S. Morrone, B. Mayer, J. Godwin, W. Xu, O. Stemmann, A. Pendas et al.
elife 2, e01133-e01133 (1 January 2013)

Shugoshin biases chromosomes for biorientation through condensin recruitment to the pericentromere
K. F. Verzijlbergen, O. O. Nerusheva, D. Kelly, A. Kerr, D. Clift, F. de Lima Alves, J. Rappsilber, and A. L. Marston
elife 3, e01374-e01374 (1 January 2013)

Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression
R. M. Ricke, K. B. Jeganathan, L. Malureanu, A. M. Harrison, and J. M. van Deursen
JCB 199, 931-949 (10 December 2012)

A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B
A. De Antoni, S. Maffini, S. Knapp, A. Musacchio, and S. Santaguida
JCB 199, 269-284 (15 October 2012)

Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation
F. Wang, N. P. Ulyanova, J. R. Daum, D. Patnaik, A. V. Kateneva, G. J. Gorbsky, and J. M. G. Higgins
JCB 199, 251-268 (15 October 2012)

Mps1 promotes rapid centromere accumulation of Aurora B
M. S. van der Waal, A. T. Saurin, M. J. M. Vromans, M. Vleugel, C. Wurzenberger, D. W. Gerlich, R. H. Medema, G. J. P. L. Kops, and S. M. A. Lens
EMBO Rep. 13, 847-854 (1 September 2012)

Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogues at inner centromeres
E. Niedzialkowska, F. Wang, P. J. Porebski, W. Minor, J. M. G. Higgins, and P. T. Stukenberg
Mol. Biol. Cell 23, 1457-1466 (15 April 2012)

Effects of phosphatase and proteasome inhibitors on Borealin phosphorylation and degradation
D. Date, M. R. Dreier, M. T. Borton, M. E. Bekier, and W. R. Taylor
J Biochem 151, 361-369 (1 April 2012)

Xenopus Shugoshin 2 regulates the spindle assembly pathway mediated by the chromosomal passenger complex
T. Rivera, C. Ghenoiu, M. Rodriguez-Corsino, S. Mochida, H. Funabiki, and A. Losada
EMBO J. 31, 1467-1479 (21 March 2012)

Contrasting roles of condensin I and condensin II in mitotic chromosome formation
L. C. Green, P. Kalitsis, T. M. Chang, M. Cipetic, J. H. Kim, O. Marshall, L. Turnbull, C. B. Whitchurch, P. Vagnarelli, K. Samejima et al.
J. Cell Sci. 125, 1591-1604 (15 March 2012)

Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction
V. Krenn, A. Wehenkel, X. Li, S. Santaguida, and A. Musacchio
JCB 196, 451-467 (20 February 2012)

PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription
D. B. Beck, H. Oda, S. S. Shen, and D. Reinberg
Genes Dev. 26, 325-337 (15 February 2012)

Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin
G. Whelan, E. Kreidl, G. Wutz, A. Egner, J.-M. Peters, and G. Eichele
EMBO J. 31, 71-82 (4 January 2012)

The Renaissance or the cuckoo clock
J. Pines, and I. Hagan
Phil Trans R Soc B 366, 3625-3634 (27 December 2011)

Spindle assembly checkpoint: the third decade
A. Musacchio, and I. Hagan
Phil Trans R Soc B 366, 3595-3604 (27 December 2011)

Aurora B dynamics at centromeres create a diffusion-based phosphorylation gradient
E. Wang, E. R. Ballister, and M. A. Lampson
JCB 194, 539-549 (22 August 2011)

Global analysis of core histones reveals nucleosomal surfaces required for chromosome bi-orientation
S. Kawashima, Y. Nakabayashi, K. Matsubara, N. Sano, T. Enomoto, K. Tanaka, M. Seki, and M. Horikoshi
EMBO J. 30, 3353-3367 (17 August 2011)

How protein kinases co-ordinate mitosis in animal cells
H. T. Ma, and R. Y. C. Poon
Biochem. J. 435, 17-31 (1 April 2011)

Temporal and Spatial Regulation of Targeting Aurora B to the Inner Centromere
Y. Watanabe, and R. Y. C. Poon
Cold Spring Harb Symp Quant Biol 0, sqb.2010.75.035v1-sqb.2010.75.035 (29 March 2011)

Kinetochore-microtubule interactions: steps towards bi-orientation
T. U. Tanaka, and R. Y. C. Poon
EMBO J. 29, 4070-4082 (15 December 2010)

Surfing Chromosomes (and Survivin)
A. Musacchio, and R. Y. C. Poon
Science 330, 183-184 (8 October 2010)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882