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

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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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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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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