Cohesin relocation from sites of chromosomal loading to places of convergent transcription (original) (raw)

Nature volume 430, pages 573–578 (2004)Cite this article

Abstract

Sister chromatids, the products of eukaryotic DNA replication, are held together by the chromosomal cohesin complex after their synthesis. This allows the spindle in mitosis to recognize pairs of replication products for segregation into opposite directions1,2,3,4,5,6. Cohesin forms large protein rings that may bind DNA strands by encircling them7, but the characterization of cohesin binding to chromosomes in vivo has remained vague. We have performed high resolution analysis of cohesin association along budding yeast chromosomes III–VI. Cohesin localizes almost exclusively between genes that are transcribed in converging directions. We find that active transcription positions cohesin at these sites, not the underlying DNA sequence. Cohesin is initially loaded onto chromosomes at separate places, marked by the Scc2/Scc4 cohesin loading complex8, from where it appears to slide to its more permanent locations. But even after sister chromatid cohesion is established, changes in transcription lead to repositioning of cohesin. Thus the sites of cohesin binding and therefore probably sister chromatid cohesion, a key architectural feature of mitotic chromosomes, display surprising flexibility. Cohesin localization to places of convergent transcription is conserved in fission yeast, suggesting that it is a common feature of eukaryotic chromosomes.

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References

  1. Michaelis, C., Ciosk, R. & Nasmyth, K. Cohesins: Chromosomal proteins that prevent premature separation of sister chromatids. Cell 91, 35–45 (1997)
    Article CAS PubMed Google Scholar
  2. Guacci, V., Koshland, D. & Strunnikov, A. A direct link between sister chromatid cohesion and chromosome condensation revealed through analysis of MCD1 in S. cerevisiae. Cell 91, 47–57 (1997)
    Article CAS PubMed PubMed Central Google Scholar
  3. Losada, A., Hirano, M. & Hirano, T. Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev. 12, 1986–1997 (1998)
    Article CAS PubMed PubMed Central Google Scholar
  4. Tomonaga, T. et al. Characterization of fission yeast cohesin: Essential anaphase proteolysis of Rad21 phosphorylated in the S phase. Genes Dev. 14, 2757–2770 (2000)
    Article CAS PubMed PubMed Central Google Scholar
  5. Tanaka, T., Fuchs, J., Loidl, J. & Nasmyth, K. Cohesin ensures bipolar attachment of microtubules to sister centromeres and resists their precocious separation. Nature Cell Biol. 2, 492–499 (2000)
    Article CAS PubMed Google Scholar
  6. Uhlmann, F. Chromosome cohesion and separation: From men and molecules. Curr. Biol. 13, R104–R114 (2003)
    Article CAS PubMed Google Scholar
  7. Haering, C. H., Löwe, J., Hochwagen, A. & Nasmyth, K. Molecular architecture of SMC proteins and the yeast cohesin complex. Mol. Cell 9, 773–788 (2002)
    Article CAS PubMed Google Scholar
  8. Ciosk, R. et al. Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins. Mol. Cell 5, 1–20 (2000)
    Article Google Scholar
  9. Blat, Y. & Kleckner, N. Cohesins bind to preferential sites along yeast chromosome III, with differential regulation along arms versus the centric region. Cell 98, 249–259 (1999)
    Article CAS PubMed Google Scholar
  10. Tanaka, T., Cosma, M. P., Wirth, K. & Nasmyth, K. Identification of cohesin association sites at centromeres and along chromosome arms. Cell 98, 847–858 (1999)
    Article CAS PubMed Google Scholar
  11. Megee, P. C. & Koshland, D. A functional assay for centromere-associated sister chromatid cohesion. Science 285, 254–257 (1999)
    Article CAS PubMed Google Scholar
  12. Laloraya, S., Guacci, V. & Koshland, D. Chromosomal addresses of the cohesin component Mcd1p. J. Cell Biol. 151, 1047–1056 (2000)
    Article CAS PubMed PubMed Central Google Scholar
  13. Nonaka, N. et al. Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast. Nature Cell Biol. 4, 89–93 (2001)
    Article ADS Google Scholar
  14. Bernard, P. et al. Requirement of heterochromatin for cohesion at centromeres. Science 294, 2539–2542 (2001)
    Article ADS CAS PubMed Google Scholar
  15. Hakimi, M.-A. et al. A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature 418, 994–997 (2002)
    Article ADS CAS PubMed Google Scholar
  16. Katou, Y. et al. S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature 424, 1078–1083 (2003)
    Article ADS CAS PubMed Google Scholar
  17. Filipski, J. & Mucha, M. Structure, function and DNA composition of Saccharomyces cerevisiae chromatin loops. Gene 300, 63–68 (2002)
    Article CAS PubMed Google Scholar
  18. Chu, S. et al. The transcriptional program of sporulation in budding yeast. Science 282, 699–705 (1998)
    Article ADS CAS PubMed Google Scholar
  19. Gasch, A. P. et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell 11, 4241–4257 (2000)
    Article CAS PubMed PubMed Central Google Scholar
  20. Tóth, A. et al. Yeast cohesin complex requires a conserved protein, Eco1p (Ctf7), to establish cohesion between sister chromatids during DNA replication. Genes Dev. 13, 320–333 (1999)
    Article PubMed PubMed Central Google Scholar
  21. Arumugam, P. et al. ATP hydrolysis is required for cohesin's association with chromosomes. Curr. Biol. 13, 1941–1953 (2003)
    Article CAS PubMed Google Scholar
  22. Sjögren, C. & Nasmyth, K. Sister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiae. Curr. Biol. 11, 991–995 (2001)
    Article PubMed Google Scholar
  23. Jacq, C. et al. The nucleotide sequence of Saccharomyces cerevisiae chromosome IV. Nature 387(suppl), 75–78 (1997)
    CAS PubMed Google Scholar
  24. Donze, D., Adams, C. R., Rine, J. & Kamakaka, R. T. The boundaries of the silenced HMR domain in Saccharomyces cerevisiae. Genes Dev. 13, 698–708 (1999)
    Article CAS PubMed PubMed Central Google Scholar
  25. Cohen, B. A., Mitra, R. D., Hughes, J. D. & Church, G. M. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nature Genet. 26, 183–186 (2000)
    Article CAS PubMed Google Scholar
  26. Weitzer, S., Lehane, C. & Uhlmann, F. A model for ATP hydrolysis-dependent binding of cohesin to DNA. Curr. Biol. 13, 1930–1940 (2003)
    Article CAS PubMed Google Scholar
  27. Toyoda, Y. et al. Requirement of chromatid cohesion proteins Rad21/Scc1 and Mis4/Scc2 for normal spindle-kinetochore interaction in fission yeast. Curr. Biol. 12, 347–358 (2002)
    Article CAS PubMed Google Scholar
  28. Waizenegger, I. C., Hauf, S., Meinke, A. & Peters, J.-M. Two distinct pathways remove mammalian cohesin complexes from chromosome arms in prophase and from centromeres in anaphase. Cell 103, 399–410 (2000)
    Article CAS PubMed Google Scholar
  29. Reid, R. J. D., Sunjevaric, I., Kedacche, M. & Rothstein, R. Efficient PCR-based gene disruption in Saccharomyces strains using intergenic primers. Yeast 19, 319–328 (2002)
    Article CAS PubMed Google Scholar
  30. Ohta, K. et al. Mutations in the MRE11, RAD50, XRS2, and MRE2 genes alter chromatin configuration at meiotic DNA double-stranded break sites in premeiotic and meiotic cells. Proc. Natl Acad. Sci. USA 95, 645–651 (1998)
    Article ADS Google Scholar

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Acknowledgements

We are indebted to E. Schwob for initiating this collaboration. We also thank A. Nakada and T. Chaplin for technical support, R. Rothstein for reagents, and J. Cau, J. Sgouros, J. Svejstrup and members of our laboratories for discussions and comments on the manuscript. A.L. was supported by an EU Marie Curie individual fellowship and a Journal of Cell Science travelling fellowship; K.S. acknowledges support through a MEXT grants-in-aid for priority areas; F.U. was supported by the EMBO Young Investigator programme.

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Author notes

  1. Katsuhiko Shirahige and Frank Uhlmann: These authors contributed equally to this work

Authors and Affiliations

  1. Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, WC2A 3PX, London, UK
    Armelle Lengronne & Frank Uhlmann
  2. Computational Genome Analysis Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, WC2A 3PX, London, UK
    Gavin P. Kelly
  3. Riken Genomic Science Center, Human Genome Research Group, Genome Informatics Team, 1-7-22-W417 Suehiro, Tsurumi, Yokohama City, Kanagawa, 230-0045, Japan
    Yuki Katou & Katsuhiko Shirahige
  4. Center for Biological Resources and Informatics, Division of Gene Research, and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8501, Japan
    Saori Mori & Katsuhiko Shirahige
  5. Science of Biological Supramolecular Systems, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan
    Saori Mori
  6. Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, 113-0032, Tokyo, Japan
    Shihori Yokobayashi & Yoshinori Watanabe
  7. Research Center for Advanced Science and Technology, Mitsubishi Research Institute Inc., 2-3-6 Ohtemachi, Chiyoda-ku, Tokyo, 100-8141, Japan
    Takehiko Itoh
  8. SORST, Japan Science and Technology Agency, Yayoi 1-1-1, Tokyo, 113-0032, Japan
    Yoshinori Watanabe

Authors

  1. Armelle Lengronne
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  2. Yuki Katou
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  3. Saori Mori
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  4. Shihori Yokobayashi
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  5. Gavin P. Kelly
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  6. Takehiko Itoh
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  7. Yoshinori Watanabe
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  8. Katsuhiko Shirahige
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  9. Frank Uhlmann
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Correspondence toFrank Uhlmann.

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Lengronne, A., Katou, Y., Mori, S. et al. Cohesin relocation from sites of chromosomal loading to places of convergent transcription.Nature 430, 573–578 (2004). https://doi.org/10.1038/nature02742

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