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Cajal Body dynamics and association with chromatin are ATP-dependent

Nature Cell Biology volume 4, pages 502–508 (2002)Cite this article

Abstract

Cajal bodies (CBs) are nuclear organelles that contain factors required for splicing, ribosome biogenesis and transcription. Our previous analysis in living cells showed that CBs are dynamic structures. Here, we show that CB mobility is described by anomalous diffusion and that bodies alternate between association with chromatin and diffusion within the interchromatin space. CB mobility increases after ATP depletion and inhibition of transcription, suggesting that the association of CB and chromatin requires ATP and active transcription. This behaviour is fundamentally different from the ATP-dependent mobility observed for chromatin and suggests that a novel mechanism governs CB, and possibly other, nuclear body dynamics.

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Figure 1: CB movement and its relation to chromatin.
Figure 2: Different types of CB movement in live HeLaGFP–coilin cells.
Figure 3: The mobility of CBs within the interchromatin space is dependent on ATP.
Figure 4: ATP depletion and transcriptional inhibition affect the mobility of CBs.
Figure 5: Anomalous diffusion of CBs requires ongoing transcription and energy.
Figure 6: CB mobility is dependent on protein synthesis and nuclear export.

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References

  1. Ramón y Cajal, S. Un sencillo metodo de coloracíon selectiva del reticulo protoplasmico. Trab. Lab. Invest. Biol. (Madrid) 2, 129–221 (1903).

    Google Scholar 

  2. Brasch, K. & Ochs, R. L. Nuclear bodies (NBs): a newly 'rediscovered' organelle. Exp. Cell Res. 202, 211–223 (1992).

    Article  CAS  Google Scholar 

  3. Gall, J. G. Cajal bodies: the first 100 years. Annu. Rev. Cell Dev. Biol. 16, 273–300 (2000).

    Article  CAS  Google Scholar 

  4. Andrade, L. E., Tan, E. M. & Chan, E. K. Immunocytochemical analysis of the coiled body in the cell cycle and during cell proliferation. Proc. Natl Acad. Sci. USA 90, 1947–1951 (1993).

    Article  CAS  Google Scholar 

  5. Matera, A. G. Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol. 9, 302–309 (1999).

    Article  CAS  Google Scholar 

  6. Sleeman, J. E. & Lamond, A. I. Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway. Curr. Biol. 9, 1065–1074 (1999).

    Article  CAS  Google Scholar 

  7. Tucker, K. E. et al. Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. J. Cell Biol. 154, 293–307 (2001).

    Article  CAS  Google Scholar 

  8. Bauer, D. W. & Gall, J. G. Coiled bodies without coilin. Mol. Biol. Cell 8, 73–82 (1997).

    Article  CAS  Google Scholar 

  9. Boudonck, K., Dolan, L. & Shaw, P. J. The movement of coiled bodies visualized in living plant cells by the green fluorescent protein. Mol. Biol. Cell 10, 2297–2307 (1999).

    Article  CAS  Google Scholar 

  10. Platani, M., Goldberg, I., Swedlow, J. R. & Lamond, A. I. In vivo analysis of Cajal body movement, separation and joining in live human cells. J. Cell. Biol. 151, 1561–1574 (2000).

    Article  CAS  Google Scholar 

  11. Snaar, S., Wiesmeijer, K., Jochemsen, A. G., Tanke, H. J. & Dirks, R. W. Mutational analysis of fibrillarin and its mobility in living human cells. J. Cell Biol. 151, 653–662 (2000).

    Article  CAS  Google Scholar 

  12. Frey, M. R. & Matera, A. G. Coiled bodies contain U7 small nuclear RNA and associate with specific DNA sequences in interphase human cells. Proc. Natl Acad. Sci. USA 92, 5915–5919 (1995).

    Article  CAS  Google Scholar 

  13. Gall, J. G., Tsvetkov, A., Wu, Z. & Murphy, C. Is the sphere organelle/coiled body a universal nuclear component? Dev. Genet. 16, 25–35 (1995).

    Article  CAS  Google Scholar 

  14. Wu, C. H. & Gall, J. G. U7 small nuclear RNA in C snurposomes of the Xenopus germinal vesicle. Proc. Natl Acad. Sci. USA 90, 6257–6259 (1993).

    Article  CAS  Google Scholar 

  15. Gao, L., Frey, M. R. & Matera, A. G. Human genes encoding U3 snRNA associate with coiled bodies in interphase cells and are clustered on chromosome 17p11.2 in a complex inverted repeat structure. Nucleic Acids Res. 25, 4740–4747 (1997).

    Article  CAS  Google Scholar 

  16. Smith, K. P., Carter, K. C., Johnson, C. V. & Lawrence, J. B. U2 and U1 snRNA gene loci associate with coiled bodies. J. Cell Biochem. 59, 473–485 (1995).

    Article  CAS  Google Scholar 

  17. Jacobs, E. Y. et al. Coiled bodies preferentially associate with U4, U11, and U12 small nuclear RNA genes in interphase HeLa cells but not with U6 and U7 genes. Mol. Biol. Cell 10, 1653–1663 (1999).

    Article  CAS  Google Scholar 

  18. Shopland, L. S. et al. Replication-dependent histone gene expression is related to Cajal body (CB) association but does not require sustained CB contact. Mol. Biol. Cell 12, 565–576 (2001).

    Article  CAS  Google Scholar 

  19. Callan, H. G., Gall, J. G. & Murphy, C. Histone genes are located at the sphere loci of Xenopus lampbrush chromosomes. Chromosoma 101, 245–251 (1991).

    Article  CAS  Google Scholar 

  20. Kanda, T., Sullivan, K. F. & Wahl, G. M. Histone–GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr. Biol. 8, 377–385 (1998).

    Article  CAS  Google Scholar 

  21. Qian, H., Sheetz, M. P. & Elson, E. L. Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys. J. 60, 910–921 (1991).

    Article  CAS  Google Scholar 

  22. Frey, M. R., Bailey, A. D., Weiner, A. M. & Matera, A. G. Association of snRNA genes with coiled bodies is mediated by nascent snRNA transcripts. Curr. Biol. 9, 126–135 (1999).

    Article  CAS  Google Scholar 

  23. Frey, M. R. & Matera, A. G. RNA-mediated interaction of Cajal bodies and U2 snRNA genes. J. Cell Biol. 154, 499–509 (2001).

    Article  CAS  Google Scholar 

  24. Morton, W. M., Ayscough, K. R. & McLaughlin, P. J. Latrunculin alters the actin-monomer subunit interface to prevent polymerization. Nature Cell Biol. 2, 376–378 (2000).

    Article  CAS  Google Scholar 

  25. Smith, P. R., Morrison, I. E., Wilson, K. M., Fernandez, N. & Cherry, R. J. Anomalous diffusion of major histocompatibility complex class I molecules on HeLa cells determined by single particle tracking. Biophys J. 76, 3331–3344 (1999).

    Article  CAS  Google Scholar 

  26. Feder, T. J., Brust-Mascher, I., Slattery, J. P., Baird, B. & Webb, W. W. Constrained diffusion or immobile fraction on cell surfaces: a new interpretation. Biophys J. 70, 2767–2773 (1996).

    Article  CAS  Google Scholar 

  27. Simson, R. et al. Structural mosaicism on the submicron scale in the plasma membrane. Biophys J. 74, 297–308 (1998).

    Article  CAS  Google Scholar 

  28. Saxton, M. J. Anomalous diffusion due to binding: a Monte Carlo study. Biophys J. 70, 1250–1262 (1996).

    Article  CAS  Google Scholar 

  29. Saxton, M. J. Anomalous diffusion due to obstacles: a Monte Carlo study. Biophys J. 66, 394–401 (1994).

    Article  CAS  Google Scholar 

  30. Fornerod, M., Ohno, M., Yoshida, M. & Mattaj, I. W. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90, 1051–1060 (1997).

    Article  CAS  Google Scholar 

  31. Cullen, B. R. Nuclear RNA export pathways. Mol. Cell Biol. 20, 4181–4187 (2000).

    Article  CAS  Google Scholar 

  32. Carvalho, T. et al. The spinal muscular atrophy disease gene product, SMN: A link between snRNP biogenesis and the Cajal (coiled) body. J. Cell Biol. 147, 715–728 (1999).

    Article  CAS  Google Scholar 

  33. Adachi, Y. & Yanagida, M. Higher order chromosome structure is affected by cold-sensitive mutations in a Schizosaccharomyces pombe gene crm1+ which encodes a 115-kD protein preferentially localized in the nucleus and its periphery. J. Cell Biol. 108, 1195–1207 (1989).

    Article  CAS  Google Scholar 

  34. Eissenberg, J. C. & Elgin, S. C. The HP1 protein family: getting a grip on chromatin. Curr. Opin. Genet. Dev. 10, 204–210 (2000).

    Article  CAS  Google Scholar 

  35. Schardin, M., Cremer, T., Hager, H. D. & Lang, M. Specific staining of human chromosomes in Chinese hamster x man hybrid cell lines demonstrates interphase chromosome territories. Human Genet. 71, 281–287 (1985).

    Article  CAS  Google Scholar 

  36. Croft, J. A. et al. Differences in the localization and morphology of chromosomes in the human nucleus. J. Cell Biol. 145, 1119–1131 (1999).

    Article  CAS  Google Scholar 

  37. Francastel, C., Walters, M. C., Groudine, M. & Martin, D. I. A functional enhancer suppresses silencing of a transgene and prevents its localization close to centrometric heterochromatin. Cell 99, 259–269 (1999).

    Article  CAS  Google Scholar 

  38. Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3, 207–217 (1999).

    Article  CAS  Google Scholar 

  39. Lundgren, M. et al. Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene. Cell 103, 733–743 (2000).

    Article  CAS  Google Scholar 

  40. Tumbar, T. & Belmont, A. S. Interphase movements of a DNA chromosome region modulated by VP16 transcriptional activator. Nature Cell Biol. 3, 134–139 (2001).

    Article  CAS  Google Scholar 

  41. Marshall, W. F. et al. Interphase chromosomes undergo constrained diffusional motion in living cells. Curr. Biol. 7, 930–939 (1997).

    Article  CAS  Google Scholar 

  42. Bornfleth, H., Edelmann, P., Zink, D., Cremer, T. & Cremer, C. Quantitative motion analysis of subchromosomal foci in living cells using four-dimensional microscopy. Biophys J. 77, 2871–2886 (1999).

    Article  CAS  Google Scholar 

  43. Marshall, W. F., Dernburg, A. F., Harmon, B., Agard, D. A. & Sedat, J. W. Specific interactions of chromatin with the nuclear envelope: positional determination within the nucleus in Drosophila melanogaster. Mol. Biol. Cell 7, 825–842 (1996).

    Article  CAS  Google Scholar 

  44. Swedlow, J. R. & Lamond, A. I. Nuclear Dynamics: where genes are and how they got there. Genome Biol. [online] (cited 09 March 2001) http://genomebiology.com/2001/2/3/reviews/0002 (2001).

  45. Vazquez, J., Belmont, A. S. & Sedat, J. W. Multiple regimes of constrained chromosome motion are regulated in the interphase Drosophila nucleus. Curr. Biol. 11, 1227–1239 (2001).

    Article  CAS  Google Scholar 

  46. Heun, P., Laroche, T., Shimada, K., Furrer, P. & Gasser, S. M. Chromosome dynamics in the yeast interphase nucleus. Science 294, 2181–2186 (2001).

    Article  CAS  Google Scholar 

  47. Muratani, M. et al. Metabolic-energy-dependent movement of PML bodies within the mammalian cell nucleus. Nature Cell Biol. 4, 106–110 (2002).

    Article  CAS  Google Scholar 

  48. Misteli, T. Protein dynamics: implications for nuclear architecture and gene expression. Science 291, 843–847 (2001).

    Article  CAS  Google Scholar 

  49. Spector, D. L. Nuclear domains. J. Cell Sci. 114, 2891–2893 (2001).

    CAS  PubMed  Google Scholar 

  50. Pederson, T. Protein mobility within the nucleus – what are the right moves? Cell 104, 635–638 (2001).

    Article  CAS  Google Scholar 

  51. Sheetz, M. P., Turney, S., Qian, H. & Elson, E. L. Nanometre-level analysis demonstrates that lipid flow does not drive membrane glycoprotein movements. Nature 340, 284–288 (1989).

    Article  CAS  Google Scholar 

  52. Saxton, M. J. Single-particle tracking: the distribution of diffusion coefficients. Biophys J. 72, 1744–1753 (1997).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank M. Saxton for discussions on anomalous diffusion, members of the Lamond lab and P. Nero for helpful discussions. We thank M. Sanders and P. Crews for supplying the latrunculin A preparation, which was supported by National Institutes of Health grant CA47135 to P. Crews. M.P. was supported by a Dame Catherine Cookson studentship and a Biotechnology and Biological Sciences Research Council Studentship. A.I.L. is a Wellcome Trust Principal Research Fellow. J.R.S. is a Wellcome Trust Career Development Fellow (054333).

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  1. Ilya Goldberg

    Present address: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, 333 Cassell Drive, Suite 4000, Baltimore, MD 21224, USA

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  1. Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Medical Sciences Institute/Wellcome Trust Biocentre, Dow street>, Dundee, DD1 5EH, Scotland

    Melpomeni Platani, Angus I. Lamond & Jason R. Swedlow

  2. Department of Biology, Massachusetts Institute of Technology, 77 Mass Avenue, Cambridge, 02139, MA, USA

    Ilya Goldberg

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Platani, M., Goldberg, I., Lamond, A. et al. Cajal Body dynamics and association with chromatin are ATP-dependent. Nat Cell Biol 4, 502–508 (2002). https://doi.org/10.1038/ncb809

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