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Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activation

Nature Cell Biology volume 12, pages 719–727 (2010)Cite this article

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Abstract

Heterochromatin protein 1 (HP1) has an essential role in heterochromatin formation and mitotic progression through its interaction with various proteins. We have identified a unique HP1α-binding protein, POGZ (pogo transposable element-derived protein with zinc finger domain), using an advanced proteomics approach. Proteins generally interact with HP1 through a PxVxL (where x is any amino-acid residue) motif; however, POGZ was found to bind to HP1α through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1α–chromatin interaction. Depletion experiments confirmed that the POGZ HP1-binding domain is essential for normal mitotic progression and dissociation of HP1α from mitotic chromosome arms. Furthermore, POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1α dissociation with Aurora B kinase activation during mitosis.

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Figure 1: Identification and classification of HPBPs.
Figure 2: POGZ interacts with HP1α and localizes to chromatin.
Figure 3: Knockdown of POGZ causes mislocalization of HP1α and the CPC.
Figure 4: Knockdown of POGZ causes defects in sister-chromatid cohesion and kinetochore protein assembly.
Figure 5: HPZ is essential for the translocation of HP1 and the CPC.

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References

  1. Fischer, T. et al. Diverse roles of HP1 proteins in heterochromatin assembly and functions in fission yeast. Proc. Natl Acad. Sci. USA 106, 8998–9003 (2009).

    Article  CAS  Google Scholar 

  2. Hediger, F. & Gasser, S. M. Heterochromatin protein 1: don't judge the book by its cover! Curr. Opin. Genet. Dev. 16, 143–150 (2006).

    Article  CAS  Google Scholar 

  3. Hiragami, K. & Festenstein, R. Heterochromatin protein 1: a pervasive controlling influence. Cell Mol. Life Sci. 62, 2711–2726 (2005).

    Article  CAS  Google Scholar 

  4. Loyola, A. et al. The HP1α–CAF1–SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep. 10, 769–775 (2009).

    Article  CAS  Google Scholar 

  5. Maison, C. & Almouzni, G. HP1 and the dynamics of heterochromatin maintenance. Nat. Rev. Mol. Cell Biol. 5, 296–304 (2004).

    Article  CAS  Google Scholar 

  6. Motamedi, M. R. et al. HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms. Mol. Cell 32, 778–790 (2008).

    Article  CAS  Google Scholar 

  7. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).

    Article  CAS  Google Scholar 

  8. Nielsen, A. L. et al. Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol. Cell 7, 729–739 (2001).

    Article  CAS  Google Scholar 

  9. Brasher, S. V. et al. The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J. 19, 1587–1597 (2000).

    Article  CAS  Google Scholar 

  10. Smothers, J. F. & Henikoff, S. The HP1 chromo shadow domain binds a consensus peptide pentamer. Curr. Biol. 10, 27–30 (2000).

    Article  CAS  Google Scholar 

  11. Thiru, A. et al. Structural basis of HP1/PxVxL motif peptide interactions and HP1 localisation to heterochromatin. EMBO J. 23, 489–499 (2004).

    Article  CAS  Google Scholar 

  12. Cheutin, T. et al. Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science 299, 721–725 (2003).

    Article  CAS  Google Scholar 

  13. Fischle, W. et al. Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438, 1116–1122 (2005).

    Article  CAS  Google Scholar 

  14. Hirota, T., Lipp, J. J., Toh, B. H. & Peters, J. M. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438, 1176–1180 (2005).

    Article  CAS  Google Scholar 

  15. Ruchaud, S., Carmena, M. & Earnshaw, W. C. Chromosomal passengers: conducting cell division. Nat. Rev. Mol. Cell Biol. 8, 798–812 (2007).

    Article  CAS  Google Scholar 

  16. Hayashi-Takanaka, Y., Yamagata, K., Nozaki, N. & Kimura, H. Visualizing histone modifications in living cells: spatiotemporal dynamics of H3 phosphorylation during interphase. J. Cell Biol. 187, 781–790 (2009).

    Article  CAS  Google Scholar 

  17. Sessa, F. et al. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol. Cell 18, 379–391 (2005).

    Article  CAS  Google Scholar 

  18. Rosasco-Nitcher, S. E., Lan, W., Khorasanizadeh, S. & Stukenberg, P. T. Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319, 469–472 (2008).

    Article  CAS  Google Scholar 

  19. Kelly, A. E. et al. Chromosomal enrichment and activation of the Aurora B pathway are coupled to spatially regulate spindle assembly. Dev. Cell 12, 31–43 (2007).

    Article  CAS  Google Scholar 

  20. Ainsztein, A. M., Kandels-Lewis, S. E., Mackay, A. M. & Earnshaw, W. C. INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. J. Cell Biol. 143, 1763–1774 (1998).

    Article  CAS  Google Scholar 

  21. Obuse, C. et al. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat. Cell Biol. 6, 1135–1141 (2004).

    Article  CAS  Google Scholar 

  22. Kiyomitsu, T., Iwasaki, O., Obuse, C. & Yanagida, M. Inner centromere formation requires hMis14, a trident kinetochore protein that specifically recruits HP1 to human chromosomes. J. Cell Biol. 188, 791–807 (2010).

    Article  CAS  Google Scholar 

  23. Lechner, M. S., Schultz, D. C., Negorev, D., Maul, G. G. & Rauscher, F. J. 3rd. The mammalian heterochromatin protein 1 binds diverse nuclear proteins through a common motif that targets the chromoshadow domain. Biochem. Biophys. Res. Commun. 331, 929–937 (2005).

    Article  CAS  Google Scholar 

  24. Tudor, M., Lobocka, M., Goodell, M., Pettitt, J. & O'Hare, K. The pogo transposable element family of Drosophila melanogaster. Mol. Gen. Genet. 232, 126–134 (1992).

    Article  CAS  Google Scholar 

  25. Bartholomeeusen, K. et al. Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of PogZ. J. Biol. Chem. 284, 11467–11477 (2009).

    Article  CAS  Google Scholar 

  26. Yamagishi, Y., Sakuno, T., Shimura, M. & Watanabe, Y. Heterochromatin links to centromeric protection by recruiting shugoshin. Nature 455, 251–255 (2008).

    Article  CAS  Google Scholar 

  27. Kitajima, T. S., Hauf, S., Ohsugi, M., Yamamoto, T. & Watanabe, Y. Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. Curr. Biol. 15, 353–359 (2005).

    Article  CAS  Google Scholar 

  28. Hauf, S., Waizenegger, I. C. & Peters, J. M. Cohesin cleavage by separase required for anaphase and cytokinesis in human cells. Science 293, 1320–1323 (2001).

    Article  CAS  Google Scholar 

  29. Cheeseman, I. M. et al. A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. Genes Dev. 18, 2255–2268 (2004).

    Article  CAS  Google Scholar 

  30. Dai, J., Sullivan, B. A. & Higgins, J. M. Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Dev. Cell 11, 741–750 (2006).

    Article  CAS  Google Scholar 

  31. Pouwels, J. et al. Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1. Cell Cycle 6, 1579–1585 (2007).

    Article  CAS  Google Scholar 

  32. Ditchfield, C. et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J. Cell Biol. 161, 267–280 (2003).

    Article  CAS  Google Scholar 

  33. Tatsumi, Y., Ohta, S., Kimura, H., Tsurimoto, T. & Obuse, C. The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1. J. Biol. Chem. 278, 41528–41534 (2003).

    Article  CAS  Google Scholar 

  34. Albritton, L. M., Tseng, L., Scadden, D. & Cunningham, J. M. A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection. Cell 57, 659–666 (1989).

    Article  CAS  Google Scholar 

  35. Kitamura, T. et al. Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp. Hematol. 31, 1007–1014 (2003).

    Article  CAS  Google Scholar 

  36. Kiyomitsu, T., Obuse, C. & Yanagida, M. Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1. Dev. Cell 13, 663–676 (2007).

    Article  CAS  Google Scholar 

  37. Taddei, A., Maison, C., Roche, D. & Almouzni, G. Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases. Nat. Cell Biol. 3, 114–120 (2001).

    Article  CAS  Google Scholar 

  38. Ishihama, Y. et al. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol. Cell Proteomics 4, 1265–1272 (2005).

    Article  CAS  Google Scholar 

  39. Ando, S., Yang, H., Nozaki, N., Okazaki, T. & Yoda, K. CENP-A, -B, and -C chromatin complex that contains the I-type α-satellite array constitutes the prekinetochore in HeLa cells. Mol. Cell Biol. 22, 2229–2241 (2002).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank D. Goto, J. Nakayama, K. Hamada, Y. Murakami, G. Almouzni and M. Yanagida for comments, Y. Shinkai, M. Tachibana, M. Yanagida, T. Kiyomitsu, K. Yoda, S. Hatakeyama, K. Hanada, T. Kitamura, A. Imura and J-M. Peters for materials, T. Iwanaga and N. Sakai for technical instruction, and E. Ono for administration. R-S.N. was supported by a JSPS (Japan Society for the Promotion of Science) special fellowship. This work was supported by grants-in-aid from MEXT (Ministry of Education, Culture, Sports, Science and Technology) of Japan, and by Inamori, Uehara Memorial, Naito, Mochida Memorial and Matrix Science K.K. Foundations (C.O.).

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  1. Osamu Iwasaki

    Present address: Present address: The Wistar Institute, Philadelphia, PA 19104, USA.,

Authors and Affiliations

  1. Graduate School of Life Science, Hokkaido University, 001-0021, Sapporo, Japan

    Ryu-Suke Nozawa, Koji Nagao, Hiro-Taka Masuda, Osamu Iwasaki & Chikashi Obuse

  2. Initial Research Project, Okinawa Institute of Science and Technology, 904-2234, Okinawa, Japan

    Koji Nagao

  3. Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), 135-8550, Tokyo, Japan

    Toru Hirota

  4. Kanagawa Dental College, 238-8580, Yokosuka, Japan

    Naohito Nozaki

  5. Graduate School of Frontier Bioscience, Osaka University, 565-0871, Suita, Japan

    Hiroshi Kimura

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Contributions

R-S.N. performed most of the experiments and analysis. K.N. analysed mass-spectrometry data. H-T.M. quantified microscopy and FRAP data with a help of H.K. O.I. generated some HP1-related constructs. T.H. provided CPC-related materials. N.N. and H.K. provided Histone H3-related antibodies. C.O. conceived the study. R-S.N., K.N., H.K. and C.O. wrote the manuscript.

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Correspondence to Chikashi Obuse.

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Nozawa, RS., Nagao, K., Masuda, HT. et al. Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activation. Nat Cell Biol 12, 719–727 (2010). https://doi.org/10.1038/ncb2075

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