Penfold, Christopher A., Brown, Paul E., Lawrence, Neil (Neil D.) and Goldman, Alastair S. H.. (2012) Modeling meiotic chromosomes indicates a size dependent contribution of telomere clustering and chromosome rigidity to homologue juxtaposition. PLoS Computational Biology, Vol.8 (No.5). e1002496. ISSN 1553-7358

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Abstract

Meiosis is the cell division that halves the genetic component of diploid cells to form gametes or spores. To achieve this, meiotic cells undergo a radical spatial reorganisation of chromosomes. This reorganisation is a prerequisite for the pairing of parental homologous chromosomes and the reductional division, which halves the number of chromosomes in daughter cells. Of particular note is the change from a centromere clustered layout (Rabl configuration) to a telomere clustered conformation (bouquet stage). The contribution of the bouquet structure to homologous chromosome pairing is uncertain. We have developed a new in silico model to represent the chromosomes of Saccharomyces cerevisiae in space, based on a worm-like chain model constrained by attachment to the nuclear envelope and clustering forces. We have asked how these constraints could influence chromosome layout, with particular regard to the juxtaposition of homologous chromosomes and potential nonallelic, ectopic, interactions. The data support the view that the bouquet may be sufficient to bring short chromosomes together, but the contribution to long chromosomes is less. We also find that persistence length is critical to how much influence the bouquet structure could have, both on pairing of homologues and avoiding contacts with heterologues. This work represents an important development in computer modeling of chromosomes, and suggests new explanations for why elucidating the functional significance of the bouquet by genetics has been so difficult.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH):	Meiosis -- Computer simulation, Saccharomyces cerevisiae -- Computer simulation, Chromosomes -- Computer simulation
Journal or Publication Title:	PLoS Computational Biology
Publisher:	Public Library of Science
ISSN:	1553-7358
Date:	2012
Volume:	Vol.8
Number:	No.5
Page Range:	e1002496
Identification Number:	10.1371/journal.pcbi.1002496
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)
References:	1. Zickler D, Kleckner N (1999) Meiotic chromosomes: integrating structure and function. Annu Rev Genet 33: 603–754. 2. Zickler D, Kleckner N (1998) The leptotene-zygotene transition of meiosis. Annu Rev Genet 32: 619–697. 3. Kleckner N, Zickler D, JonesGH, Dekker J, Padmore R, et al. (2004) A mechanical basis for chromosome function. Proc Natl Acad Sci U S A 101: 12592–12597. 4. Rabl FE (1885) Uber Zellteilung. Morphologishes Jarbuch 10: 214–330. 5. Shaw PJ, Abranches R, Paula Santos A, Beven AF, Stoger E, et al. (2002) The architecture of interphase chromosomes and nucleolar transcription sites in plants. J Struct Biol 140: 31–38. 6. Dong F, Jiang J (1998) Non-Rabl patterns of centromere and telomere distribution in the interphase nuclei of plant cells. Chromosome Res 6: 551–558. 7. Santos AP, Abranches R, Stoger E, Beven A, Viegas W, et al. (2002) The architecture of interphase chromosomes and gene positioning are altered by changes in DNA methylation and histone acetylation. J Cell Sci 115: 4597–4605. 8. Cowan CR, Carlton PM, Cande WZ (2001) The polar arrangement of telomeres in interphase and meiosis. Rabl organization and the bouquet. Plant Physiol 125: 532–538. 9. Tanabe H, Habermann FA, Solovei I, Cremer M, Cremer T (2002) Nonrandom radial arrangements of interphase chromosome territories: evolutionary considerations and functional implications. Mutat Res 504: 37–45. 10. Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2: 292–301. 11. Leitch AR (2000) Higher levels of organization in the interphase nucleus of cycling and differentiated cells. Microbiol Mol Biol Rev 64: 138–152. 12. Hadlaczky G, Went M, Ringertz NR (1986) Direct evidence for the non-random localization of mammalian chromosomes in the interphase nucleus. Exp Cell Res 167: 1–15. 13. Jin Q, Trelles-Sticken E, Scherthan H, Loidl J (1998) Yeast nuclei display prominent centromere clustering that is reduced in nondividing cells and in meiotic prophase. J Cell Biol 141: 21–29. 14. Burgess SM, Kleckner N (1999) Collisions between yeast chromosomal loci in vivo are governed by three layers of organization. Genes Dev 13: 1871–1883. 15. Jin QW, Fuchs J, Loidl J (2000) Centromere clustering is a major determinant of yeast interphase nuclear organization. J Cell Sci 113(Pt 11): 1903–1912. 16. Guacci V, Hogan E, Koshland D (1997) Centromere position in budding yeast: evidence for anaphase A. Mol Biol Cell 8: 957–972. 17. Duan Z, Andronescu M, Schutz K, McIlwain S, Kim YJ, et al. (2010) A threedimensional model of the yeast genome. Nature 465: 363–367. 18. Scherthan H (2001) A bouquet makes ends meet. Nat Rev Mol Cell Biol 2: 621–627. 19. Harper L, Golubovskaya I, Cande WZ (2004) A bouquet of chromosomes. J Cell Sci 117: 4025–4032. 20. Zickler D (2006) From early homologue recognition to synaptonemal complex formation. Chromosoma 115: 158–174. 21. Naranjo T, Corredor E (2008) Nuclear architecture and chromosome dynamics in the search of the pairing partner in meiosis in plants. Cytogenet Genome Res 120: 320–330. 22. Martinez-Perez E, Shaw P, Reader S, Aragon-Alcaide L, Miller T, et al. (1999) Homologous chromosome pairing in wheat. J Cell Sci 112(Pt 11): 1761–1769. 23. Chikashige Y, Ding DQ, Imai Y, Yamamoto M, Haraguchi T, et al. (1997) Meiotic nuclear reorganization: switching the position of centromeres and telomeres in the fission yeast Schizosaccharomyces pombe. Embo J 16: 193–202. 24. Obeso D, Dawson DS (2010) Temporal characterization of homologyindependent centromere coupling in meiotic prophase. PLoS One 5: e10336. 25. Bass HW, Marshall WF, Sedat JW, Agard DA, Cande WZ (1997) Telomeres cluster de novo before the initiation of synapsis: a three- dimensional spatial analysis of telomere positions before and during meiotic prophase. J Cell Biol 137: 5–18. 26. Koszul R, Kleckner N (2009) Dynamic chromosome movements during meiosis: a way to eliminate unwanted connections? Trends Cell Biol 19: 716–724. 27. Hiraoka Y, Dernburg AF (2009) The SUN rises on meiotic chromosome dynamics. Dev Cell 17: 598–605. 28. Sato A, Isaac B, Phillips CM, Rillo R, Carlton PM, et al. (2009) Cytoskeletal forces span the nuclear envelope to coordinate meiotic chromosome pairing and synapsis. Cell 139: 907–919. 29. Trelles-Sticken E, Adelfalk C, Loidl J, Scherthan H (2005) Meiotic telomere clustering requires actin for its formation and cohesin for its resolution. J Cell Biol 170: 213–223. 30. Laroche T, Martin SG, Gotta M, Gorham HC, Pryde FE, et al. (1998) Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr Biol 8: 653–656. 31. Conrad MN, Dominguez AM, Dresser ME (1997) Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast. Science 276: 1252–1255. 32. Chua PR, Roeder GS (1997) Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference. Genes Dev 11: 1786–1800. 33. Conrad MN, Lee CY, Chao G, Shinohara M, Kosaka H, et al. (2008) Rapid telomere movement in meiotic prophase is promoted by NDJ1, MPS3, and CSM4 and is modulated by recombination. Cell 133: 1175–1187. 34. Galy V, Olivo-Marin JC, Scherthan H, Doye V, Rascalou N, et al. (2000) Nuclear pore complexes in the organization of silent telomeric chromatin. Nature 403: 108–112. 35. Scherthan H, Trelles-Sticken E (2008) Absence of yKu/Hdf1 but not myosinlike proteins alters chromosome dynamics during prophase I in yeast. Differentiation 76: 91–98. 36. Conrad MN, Lee CY, Wilkerson JL, Dresser ME (2007) MPS3 mediates meiotic bouquet formation in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 104: 8863–8868. 37. Wanat JJ, Kim KP, Koszul R, Zanders S, Weiner B, et al. (2008) Csm4, in collaboration with Ndj1, mediates telomere-led chromosome dynamics and recombination during yeast meiosis. PLoS Genet 4: e1000188. 38. Trelles-Sticken E, Loidl J, Scherthan H (1999) Bouquet formation in budding yeast: initiation of recombination is not required for meiotic telomere clustering. J Cell Sci 112: 651–658. 39. Wu HY, Burgess SM (2006) Ndj1, a telomere-associated protein, promotes meiotic recombination in budding yeast. Mol Cell Biol 26: 3683–3694. 40. Kosaka H, Shinohara M, Shinohara A (2008) Csm4-dependent telomere movement on nuclear envelope promotes meiotic recombination. PLoS Genet 4: e1000196. 41. Scherthan H, Wang H, Adelfalk C, White EJ, Cowan C, et al. (2007) Chromosome mobility during meiotic prophase in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 104: 16934–16939. 42. Trelles-Sticken E, Dresser ME, Scherthan H (2000) Meiotic telomere protein Ndj1p is required for meiosis-specific telomere distribution, bouquet formation and efficient homologue pairing. J Cell Biol 151: 95–106. 43. Tomita K, Cooper JP (2007) The telomere bouquet controls the meiotic spindle. Cell 130: 113–126. 44. Koszul R, Kim KP, Prentiss M, Kleckner N, Kameoka S (2008) Meiotic chromosomes move by linkage to dynamic actin cables with transduction of force through the nuclear envelope. Cell 133: 1188–1201. 45. Cowan CR, Cande WZ (2002) Meiotic telomere clustering is inhibited by colchicine but does not require cytoplasmic microtubules. J Cell Sci 115: 3747–3756. 46. Carlton PM, Cowan CR, Cande WZ (2003) Directed motion of telomeres in the formation of the meiotic bouquet revealed by time course and simulation analysis. Mol Biol Cell 14: 2832–2843. 47. Cowan CR, Carlton PM, Cande WZ (2002) Reorganization and polarization of the meiotic bouquet-stage cell can be uncoupled from telomere clustering. J Cell Sci 115: 3757–3766. 48. Chen W, Jinks-Robertson S (1998) Mismatch repair proteins regulate heteroduplex formation during mitotic recombination in yeast. Mol Cell Biol 18: 6525–6537. 49. Datta A, Adjiri A, New L, Crouse GF, Jinks Robertson S (1996) Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccaromyces cerevisiae. Mol Cell Biol 16: 1085–1093. 50. Selva EM, New L, Crouse GF, Lahue RS (1995) Mismatch correction acts as a barrier to homeologous recombination in Saccharomyces cerevisiae. Genetics 139: 1175–1188. 51. Murti JR, Bumbulis M, Schimenti JC (1994) Gene conversion between unlinked sequences in the germline of mice. Genetics 137: 837–843. 52. Haber JE, Leung WY, Borts RH, Lichten M (1991) The frequency of meiotic recombination in yeast is independent of the number and position of homologous donor sequences: implications for chromosome pairing. Proc Natl Acad Sci U S A 88: 1120–1124. 53. Jinks-Robertson S, Petes TD (1986) Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes. Genetics 114: 731–752. 54. Lichten M, Borts RH, Haber JE (1987) Meiotic gene conversion and crossing over between dispersed homologous sequences occurs frequently in Saccharomyces cerevisiae. Genetics 115: 233–246. 55. Freitas-Junior LH, Bottius E, Pirrit LA, Deitsch KW, Scheidig C, et al. (2000) Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407: 1018–1022. 56. Lim JK, Simmons MJ (1994) Gross chromosome rearrangements mediated by transposable elements in Drosophila melanogaster. Bioessays 16: 269–275. 57. Montgomery EA, Huang SM, Langley CH, Judd BH (1991) Chromosome rearrangement by ectopic recombination in Drosophila melanogaster: genome structure and evolution. Genetics 129: 1085–1098. 58. Goldman ASH, Lichten M (1996) The efficiency of meiotic recombination between dispersed sequences in Saccharomyces cerevisiae depends upon their chromosomal location. Genetics 144: 43–55. 59. Goldman ASH, Lichten M (2000) Restriction of ectopic recombination by interhomolog interactions during Saccharomyces cerevisiae meiosis. Proc Natl Acad Sci U S A 97: 9537–9542. 60. Schlecht HB, Lichten M, Goldman ASH (2004) Compartmentalization of the yeast meiotic nucleus revealed by analysis of ectopic recombination. Genetics 168: 1189–203. 61. Peoples TL, Dean E, Gonzalez O, Lambourne L, Burgess SM (2002) Close, stable homolog juxtaposition during meiosis in budding yeast is dependent on meiotic recombination, occurs independently of synapsis, and is distinct from DSB-independent pairing contacts. Genes Dev 16: 1682–1695. 62. Bystricky K, Heun P, Gehlen L, Langowski J, Gasser SM (2004) Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques. Proc Natl Acad Sci U S A 101: 16495–16500. 63. Rosa A, Everaers R (2008) Structure and dynamics of interphase chromosomes. PLoS Comput Biol 4: e1000153. 64. Gehlen LR, Rosa A, Klenin K, Langowski J, Gasser SM, et al. (2006) Spatially confined polymer chains: implications of chromatin fibre flexibility and peripheral anchoring on telomere–telomere interaction. J Phys Condens Matter 18: S245–S252. 65. Therizols P, Duong T, Dujon B, Zimmer C, Fabre E (2010) Chromosome arm length and nuclear constraints determine the dynamic relationship of yeast subtelomeres. Proc Natl Acad Sci U S A 107: 2025–2030. 66. Karpova TS, Chen TY, Sprague BL, McNally JG (2004) Dynamic interactions of a transcription factor with DNA are accelerated by a chromatin remodeller. EMBO Rep 5: 1064–1070. 67. Jorgensen P, Edgington NP, Schneider BL, Rupes I, Tyers M, et al. (2007) The size of the nucleus increases as yeast cells grow. Mol Biol Cell 18: 3523–3532. 68. Dekker J (2008) Mapping in vivo chromatin interactions in yeast suggests an extended chromatin fiber with regional variation in compaction. J Biol Chem 283: 34532–34540. 69. Morrison G, Thirumalai D (2009) Semiflexible chains in confined spaces. PhysRev E Stat Nonlin Soft Matter Phys 79: 011924. 70. Lorenz A, Fuchs J, Burger R, Loidl J (2003) Chromosome pairing does not contribute to nuclear architecture in vegetative yeast cells. Eukaryot Cell 2: 856–866. 71. Weiner BM, Kleckner N (1994) Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell 77: 977–991. 72. Loidl J, Klein F, Scherthan H (1994) Homologous pairing is reduced but not abolished in asynaptic mutants of yeast. J Cell Biol 125: 1191–1200. 73. de Lange T (1998) Ending up with the right partner. Nature 392: 753–754. 74. Zimmer C, Fabre E (2011) Principles of chromosomal organization: lessons from yeast. J Cell Biol 192: 723–733. 75. Kreth G, Finsterle J, von Hase J, Cremer M, Cremer C (2004) Radial arrangement of chromosome territories in human cell nuclei: a computer model approach based on gene density indicates a probabilistic global positioning code. Biophys J 86: 2803–2812. 76. Spakowitz AJ, Wang ZG (2005) DNA packaging in bacteriophage: is twist important? Biophys J 88: 3912–3923. 77. Ponomarev AL, Sachs RK (2001) Radiation breakage of DNA: a model based on random-walk chromatin structure. J Math Biol 43: 356–376. 78. Gennes PGD (1979) Scaling Concepts in Polymer Physics Cornell University Press. 324 p. 79. Doi M, Edwards SF (1988) The Theory of Polymer Dynamics. USA: Oxford University Press. 408 p. 80. Kawakatsu T (2004) Statistical physics of polymers: an introduction. Berlin, Heidelberg: Springer-Verlag. 216 p. 81. Kleinert H (2009) Path Integrals in Quantum Mechanics, Statistics, Polymer Physics, and Financial Markets. World Scientific Publishing Company. 1624 p. 82. Yamakawa H (1971) Modern theory of polymer solutions. Harper & Row. 83. Dekker J, Rippe K, Dekker M, Kleckner N (2002) Capturing chromosome conformation. Science 295: 1306–1311. 84. Marko JF, Siggia ED (1997) Polymer models of meiotic and mitotic chromosomes. Mol Biol Cell 8: 14. 85. Ostashevsky J (2002) A polymer model for large-scale chromatin organization in lower eukaryotes. Mol Biol Cell 13: 12. 86. Goto B, Okazaki K, Niwa O (2001) Cytoplasmic microtubular system implicated in de novo formation of a Rabl-like orientation of chromosomes in fission yeast. J Cell Sci 114: 2427–2435. 87. Poirier MG, Marko JF (2002) Micromechanical studies of mitotic chromosomes. J Muscle Res Cell Motil 23: 22. 88. Padmore R, Cao L, Kleckner N (1991) Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell 66: 1239–1256. 89. Lichten M, Goyon C, Schultes NP, Treco D, Szostak JW, et al. (1990) Detection of heteroduplex DNA molecules among the products of Saccharomyces cerevisiae meiosis. Proc Natl Acad Sci U S A 87: 7653–7657.
URI:	http://wrap.warwick.ac.uk/id/eprint/49440

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