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Nature Genetics | Article

日本語要約

Arabidopsis meiotic crossover hot spots overlap with H2A.Z nucleosomes at gene promoters

Journal name:
Nature Genetics
Volume:
45,
Pages:
1327–1336
Year published:
DOI:
doi:10.1038/ng.2766
Received
Accepted
Published online

Abstract

PRDM9 directs human meiotic crossover hot spots to intergenic sequence motifs, whereas budding yeast hot spots overlap regions of low nucleosome density (LND) in gene promoters. To investigate hot spots in plants, which lack PRDM9, we used coalescent analysis of genetic variation in Arabidopsis thaliana. Crossovers increased toward gene promoters and terminators, and hot spots were associated with active chromatin modifications, including H2A.Z, histone H3 Lys4 trimethylation (H3K4me3), LND and low DNA methylation. Hot spot–enriched A-rich and CTT-repeat DNA motifs occurred upstream and downstream, respectively, of transcriptional start sites. Crossovers were asymmetric around promoters and were most frequent over CTT-repeat motifs and H2A.Z nucleosomes. Pollen typing, segregation and cytogenetic analysis showed decreased numbers of crossovers in the arp6 H2A.Z deposition mutant at multiple scales. During meiosis, H2A.Z forms overlapping chromosomal foci with the DMC1 and RAD51 recombinases. As arp6 reduced the number of DMC1 or RAD51 foci, H2A.Z may promote the formation or processing of meiotic DNA double-strand breaks. We propose that gene chromatin ancestrally designates hot spots within eukaryotes and PRDM9 is a derived state within vertebrates.

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  1. Meiotic crossover frequency in the Arabidopsis genome.
    Figure 1: Meiotic crossover frequency in the Arabidopsis genome.

    (a) Plots showing the crossover frequency (cM/Mb) along chromosome 1 estimated by MergeMap (black), Interval (black), Interval plotted using MergeMap markers (red) and the overlay of the MergeMap and Interval maps. MergeMap was generated previously from an analysis of genotype data from 17 F2 populations33 using the MergeMap program35, 84. The 'bin' widths are variable because they are determined by intermarker distances. Horizontal dotted lines represent the mean crossover frequencies, the vertical dashed lines represent centromeres, and the vertical ticks above the x axis indicate the positions of R genes. (b) Mean crossover frequency (cM/Mb) estimated by Interval as a proportion along the length of the chromosome arms, orientated with the telomere (Tel) at 0 and the centromere (Cen) at 1 on the x axis. (c) The proportion of the crossovers estimated by Interval plotted against the proportion of the physical sequence (solid black line). The dashed line represents a uniform relationship between the genetic and physical maps.

  2. Chromatin landscape at hot and cold promoters.
    Figure 2: Chromatin landscape at hot and cold promoters.

    (a) Plots showing the mean value of the variable indicated at exons (black) and introns (red) at increasing position numbers relative to the TSS. (b) Plots showing summed, normalized values for the variable indicated across ±2-kb windows centered on hot TSSs (red), cold TSSs (blue) or random positions (black). All hot and cold distributions are significantly different by Wilcoxon signed-rank test (P < 1 × 10−15). (c) Plots are as for the hot TSS plots in b but with the indicated variables, H2A.Z45 (red), LND47 (green), H3K4me3 (ref. 44) (purple) and DNA methylation48 (blue), overlaid with cM/Mb (black). The graph on the far left shows an overlay of all the variables.

  3. A-rich and CTT-repeat DNA sequence motifs at hot and cold promoters.
    Figure 3: A-rich and CTT-repeat DNA sequence motifs at hot and cold promoters.

    (a) Logo plot for a 13-bp A-rich motif identified as being enriched at hot spot–associated promoters. (b) Enrichment of the A-rich motif shown in a at hot (red) and cold (blue) promoters in ±2-kb windows centered on the TSS and permutated (random; black) promoter sequences. (c) Crossover frequency (cM/Mb) in ±2-kb windows centered on the start coordinate of matches to the motif shown in a (red) compared to the same number of random positions (black), which were significantly different by a Wilcoxon rank-sum test (P < 1 × 10−15). (d) Enrichment of the A-rich motif (black) shown in a at hot spot–associated promoters overlaid with crossover frequency (cM/Mb; red), LND47 (red) and H2A.Z45 (red) over ±2-kb windows centered on the TSS. (e) Logo plot for a 12-bp CTT-repeat motif identified as being enriched at hot spot promoters. (f) Enrichment of the CTT-repeat motif shown in e at hot (red) and cold (blue) promoters in ±2-kb windows centered on the TSS and permutated promoter sequences (random; black). (g) Crossover frequency (cM/Mb) in ±2-kb windows centered on the start coordinate of matches to the motif shown in e (red) compared to the same number of random positions (black), which were significantly different by a Wilcoxon rank-sum test (P < 1 × 10−15). (h) Enrichment of the CTT-repeat motif (black) shown in e at hot spot promoters overlaid with crossover frequency (cM/Mb; red), LND47 (red) and H2A.Z45 (red) over ±2-kb windows centered on the TSS.

  4. The arp6 mutant has decreased crossover frequency at the 3a and 3b hot spots.
    Figure 4: The arp6 mutant has decreased crossover frequency at the 3a and 3b hot spots.

    (a,b) Plots showing crossover frequency (cM/Mb) estimated by pollen typing in wild-type plants and arp6 mutants and by Interval across the 3a (a) and 3b (b) hot spots on chromosome 3. Vertical black lines in the pollen-typing plots indicate the inner allele-specific primer positions. Red vertical ticks above the x axis indicate SNP positions. Black and red arrows represent forward- and reverse-strand genes, respectively. The associated gene numbers are shown above the arrows. Vertical dashed blue lines indicate the positions of TSSs and TTSs. Horizontal dotted lines indicate the chromosome average recombination rate. (c,d) LND ChIP-chip47, H3K4me3 ChIP-chip44 and H2A.Z ChIP-seq45 data plotted across the 3a and 3b hot spots, with plot annotations as in a and b. (e) Crossover frequencies for the hot spots 3a and 3b calculated by single-molecule pollen typing of crossover and parental molecules in wild-type plants and arp6 mutants and the associated s.d. values. Crossover rates are significantly lower in arp6 mutants (t-test; 3a, P < 1 × 10−15; 3b, P < 1 × 10−15). (f) The crossover frequencies for hot spots 3a and 3b measured by pollen-typing qPCR are significantly lower in arp6 mutants (t-test; 3a, P = 3.33 × 10−3; 3b, P = 2.95 × 10−4). Box plots show the median and the first and third quartiles of the data, and whiskers show the maximum and minimum data points. Each sample was analyzed using three technical replicates of three biological replicates.

  5. The arp6 mutant has decreased crossover frequency at the domain and whole-chromosome scales.
    Figure 5: The arp6 mutant has decreased crossover frequency at the domain and whole-chromosome scales.

    (a) Crossover frequency estimated by Interval (cM/Mb; red) plotted along chromosomes 1, 3 and 5. Physical intervals in which we measured genetic distance are labeled and indicated by gray shading. Vertical dashed lines indicate centromeres, and horizontal dashed lines indicate the chromosome mean crossover frequency. (b) Genetic distances (cM) for the intervals TEL1a, I1a, I1b, I5a, I1fg, 420 and CEN3 in wild-type plants and arp6 mutants. χ2 test P values comparing wild-type plants to arp6 mutants are shown above the plots. All temperatures were 21 °C except those listed as 12 °C. Information about sample n numbers is listed in Supplementary Tables 9,10,11,12,13,14,15. (c) The F2 genetic map length for chromosome 1 is reduced in arp6 mutants relative to wild-type plants (n = 768 for both genotypes). The number of crossovers (COs) per F2 individual was significantly lower in arp6 mutants (χ2 test P = 1.06 × 10−7). Wild-type and arp6 genetic maps are connected at SSLP marker positions, and intervals containing the centromeres are marked with red dots. (d) Histograms for chiasma numbers per meiocyte for wild-type plants and arp6 mutants using alleles in the Col (suf3) and Ler (esd1) accessions (n = 20 per genotype). There were significantly fewer chiasmata in arp6 mutants (Conway-Maxwell-Poisson regression testing; Col, P = 0.004; Ler, P = 8.0 × 10−5). On the right are representative images from n = 20 replicates of metaphase I meiocytes that were stained with DAPI and labeled by FISH against 45S (green) and 5S (red) rDNA to identify specific chromosomes. Chromosomes are labeled with their number. In wild-type plants, all bivalents except chromosome 2 are 'rings' with more than one chiasma, whereas in arp6 mutants, all bivalents except chromosome 2 are 'rods' with one chiasma. Scale bars, 10 μM.

  6. Immunolocalization of H2A.Z and meiotic proteins in wild-type plants and arp6 mutants.
    Figure 6: Immunolocalization of H2A.Z and meiotic proteins in wild-type plants and arp6 mutants.

    (a) The strand-invasion recombinases RAD51 and DMC1 (red) localize as foci to ASY1-labeled (green), DAPI-stained (blue) leptotene chromosomes in wild-type plants and arp6 mutants. MLH1 (red), a marker for crossover sites, localizes to ZYP1-labeled (green), DAPI-stained (blue) pachytene chromosomes in wild-type plants and arp6 mutants. (b) Plots showing RAD51, DMC1 and MLH1 foci numbers per meiocyte in wild-type plants and arp6 mutants. The Wilcoxon rank-sum test P values are indicated for RAD51 and DMC1 counts per meiocyte between wild-type plants and arp6 mutants in either the Col or Ler accession. As the MLH1 count data were underdispersed compared to the expectation based on the Poisson distribution, we used Conway-Maxwell-Poisson regression testing. The numbers of MLH1 foci were significantly reduced in arp6 mutants (P = 0.039) across both the Col and Ler accessions. All samples were analyzed from groups of n = 20 replicates. (c) Immunodetection of H2A.Z-GFP (red) in somatic and meiotic (leptotene) nuclei in complementing H2A.Z-GFP lines60. During meiosis, H2A.Z-GFP (red) forms discrete foci on ASY1-labeled (green), DAPI-stained (blue) chromosomes, which overlap with RAD51 and DMC1 foci (green) but are not detected in arp6 mutants. Scale bars (a,c), 10 μM.

References

  1. Kauppi, L., Jeffreys, A.J. & Keeney, S. Where the crossovers are: recombination distributions in mammals. Nat. Rev. Genet. 5, 413–424 (2004).
  2. McVean, G.A.T. et al. The fine-scale structure of recombination rate variation in the human genome. Science 304, 581–584 (2004).
  3. Pan, J. et al. A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation. Cell 144, 719–731 (2011).
  4. Baudat, F. et al. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327, 836–840 (2010).
  5. Myers, S. et al. Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science 327, 876–879 (2010).
  6. Berg, I.L. et al. Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations. Proc. Natl. Acad. Sci. USA 108, 12378–12383 (2011).
  7. Berg, I.L. et al. PRDM9 variation strongly influences recombination hot spot activity and meiotic instability in humans. Nat. Genet. 42, 859–863 (2010).
  8. Hinch, A.G. et al. The landscape of recombination in African Americans. Nature 476, 170–175 (2011).
  9. Kong, A. et al. Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467, 1099–1103 (2010).
  10. Parvanov, E.D., Petkov, P.M. & Paigen, K. Prdm9 controls activation of mammalian recombination hotspots. Science 327, 835 (2010).
  11. Smagulova, F. et al. Genome-wide analysis reveals novel molecular features of mouse recombination hotspots. Nature 472, 375–378 (2011).
  12. Myers, S., Bottolo, L., Freeman, C., McVean, G. & Donnelly, P. A fine-scale map of recombination rates and hotspots across the human genome. Science 310, 321–324 (2005).
  13. Hayashi, K., Yoshida, K. & Matsui, Y. A histone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature 438, 374–378 (2005).
  14. Grey, C. et al. Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination. PLoS Biol. 9, e1001176 (2011).
  15. Brick, K., Smagulova, F., Khil, P., Camerini-Otero, R.D. & Petukhova, G.V. Genetic recombination is directed away from functional genomic elements in mice. Nature 485, 642–645 (2012).
  16. Ohta, K., Shibata, T. & Nicolas, A. Changes in chromatin structure at recombination initiation sites during yeast meiosis. EMBO J. 13, 5754–5763 (1994).
  17. Wu, T.C. & Lichten, M. Meiosis-induced double-strand break sites determined by yeast chromatin structure. Science 263, 515–518 (1994).
  18. Fan, Q.Q. & Petes, T.D. Relationship between nuclease-hypersensitive sites and meiotic recombination hot spot activity at the HIS4 locus of Saccharomyces cerevisiae. Mol. Cell. Biol. 16, 2037–2043 (1996).
  19. Nicolas, A., Treco, D., Schultes, N.P. & Szostak, J.W. An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae. Nature 338, 35–39 (1989).
  20. Baudat, F. & Nicolas, A. Clustering of meiotic double-strand breaks on yeast chromosome III. Proc. Natl. Acad. Sci. USA 94, 5213–5218 (1997).
  21. Berchowitz, L.E., Hanlon, S.E., Lieb, J.D. & Copenhaver, G.P. A positive but complex association between meiotic double-strand break hotspots and open chromatin in Saccharomyces cerevisiae. Genome Res. 19, 2245–2257 (2009).
  22. Borde, V. et al. Histone H3 lysine 4 trimethylation marks meiotic recombination initiation sites. EMBO J. 28, 99–111 (2009).
  23. Sommermeyer, V., Béneut, C., Chaplais, E., Serrentino, M.E. & Borde, V. Spp1, a member of the Set1 complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes. Mol. Cell 49, 43–54 (2013).
  24. Sollier, J. et al. Set1 is required for meiotic S-phase onset, double-strand break formation and middle gene expression. EMBO J. 23, 1957–1967 (2004).
  25. Acquaviva, L. et al. The COMPASS subunit Spp1 links histone methylation to initiation of meiotic recombination. Science 339, 215–218 (2013).
  26. Tischfield, S.E. & Keeney, S. Scale matters: the spatial correlation of yeast meiotic DNA breaks with histone H3 trimethylation is driven largely by independent colocalization at promoters. Cell Cycle 11, 1496–1503 (2012).
  27. Copenhaver, G.P. et al. Genetic definition and sequence analysis of Arabidopsis centromeres. Science 286, 2468–2474 (1999).
  28. Dooner, H.K. Genetic fine structure of the BRONZE locus in maize. Genetics 113, 1021–1036 (1986).
  29. Giraut, L. et al. Genome-wide crossover distribution in Arabidopsis thaliana meiosis reveals sex-specific patterns along chromosomes. PLoS Genet. 7, e1002354 (2011).
  30. Gore, M.A. et al. A first-generation haplotype map of maize. Science 326, 1115–1117 (2009).
  31. Mayer, K.F.X. et al. A physical, genetic and functional sequence assembly of the barley genome. Nature 491, 711–716 (2012).
  32. Saintenac, C. et al. Detailed recombination studies along chromosome 3B provide new insights on crossover distribution in wheat (Triticum aestivum L.). Genetics 181, 393–403 (2009).
  33. Salomé, P.A. et al. The recombination landscape in Arabidopsis thaliana F2 populations. Heredity 108, 447–455 (2012).
  34. Cao, J. et al. Whole-genome sequencing of multiple Arabidopsis thaliana populations. Nat. Genet. 43, 956–963 (2011).
  35. Yelina, N.E. et al. Epigenetic remodeling of meiotic crossover frequency in Arabidopsis thaliana DNA methyltransferase mutants. PLoS Genet. 8, e1002844 (2012).
  36. Loudet, O., Chaillou, S., Camilleri, C., Bouchez, D. & Daniel-Vedele, F. Bay-0 × Shahdara recombinant inbred line population: a powerful tool for the genetic dissection of complex traits in. Arabidopsis. Theor. Appl. Genet. 104, 1173–1184 (2002).
  37. Fransz, P.F. et al. Integrated cytogenetic map of chromosome arm 4S of A. thaliana: structural organization of heterochromatic knob and centromere region. Cell 100, 367–376 (2000).
  38. Horton, M.W. et al. Genome-wide patterns of genetic variation in worldwide Arabidopsis thaliana accessions from the RegMap panel. Nat. Genet. 44, 212–216 (2012).
  39. Auton, A. et al. A fine-scale chimpanzee genetic map from population sequencing. Science 336, 193–198 (2012).
  40. Fearnhead, P. SequenceLDhot: detecting recombination hotspots. Bioinformatics 22, 3061–3066 (2006).
  41. Drouaud, J. & Mézard, C. Characterization of meiotic crossovers in pollen from Arabidopsis thaliana. Methods Mol. Biol. 745, 223–249 (2011).
  42. Bickel, P.J., Boley, N., Brown, J.B., Huang, H. & Zhang, N.R. Subsampling methods for genomic inference. Ann. Appl. Stat. 4, 1660–1697 (2010).
  43. Venters, B.J. & Pugh, B.F. How eukaryotic genes are transcribed. Crit. Rev. Biochem. Mol. Biol. 44, 117–141 (2009).
  44. Zhang, X., Bernatavichute, Y.V., Cokus, S., Pellegrini, M. & Jacobsen, S.E. Genome-wide analysis of mono-, di- and trimethylation of histone H3 lysine 4 in Arabidopsis thaliana. Genome Biol. 10, R62 (2009).
  45. Coleman-Derr, D. & Zilberman, D. Deposition of histone variant H2A.Z within gene bodies regulates responsive genes. PLoS Genet. 8, e1002988 (2012).
  46. Deal, R.B. & Henikoff, S. Histone variants and modifications in plant gene regulation. Curr. Opin. Plant Biol. 14, 116–122 (2011).
  47. Zhang, X. et al. Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis. PLoS Biol. 5, e129 (2007).
  48. Cokus, S.J. et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452, 215–219 (2008).
  49. Maloisel, L. & Rossignol, J.L. Suppression of crossing-over by DNA methylation in Ascobolus. Genes Dev. 12, 1381–1389 (1998).
  50. Bailey, T.L. et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 37, W202–W208 (2009).
  51. Bembom, O., Keles, S. & van der Laan, M.J. Supervised detection of conserved motifs in DNA sequences with cosmo. Stat. Appl. Genet. Mol. Biol. 6, Article8 (2007).
  52. Mahony, S., Golden, A., Smith, T.J. & Benos, P.V. Improved detection of DNA motifs using a self-organized clustering of familial binding profiles. Bioinformatics 21 (suppl. 1), i283–i291 (2005).
  53. Pavesi, G., Mauri, G. & Pesole, G. An algorithm for finding signals of unknown length in DNA sequences. Bioinformatics 17 (suppl. 1), S207–S214 (2001).
  54. Field, Y. et al. Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLOS Comput. Biol. 4, e1000216 (2008).
  55. Baudat, F. & de Massy, B. Cis- and trans-acting elements regulate the mouse Psmb9 meiotic recombination hotspot. PLoS Genet. 3, e100 (2007).
  56. Cole, F., Keeney, S. & Jasin, M. Comprehensive, fine-scale dissection of homologous recombination outcomes at a hot spot in mouse meiosis. Mol. Cell 39, 700–710 (2010).
  57. Jeffreys, A.J. & Neumann, R. Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. Hum. Mol. Genet. 14, 2277–2287 (2005).
  58. Choi, K. et al. SUPPRESSOR OF FRIGIDA3 encodes a nuclear ACTIN-RELATED PROTEIN6 required for floral repression in Arabidopsis. Plant Cell 17, 2647–2660 (2005).
  59. Deal, R.B., Topp, C.N., McKinney, E.C. & Meagher, R.B. Repression of flowering in Arabidopsis requires activation of FLOWERING LOCUS C expression by the histone variant H2A.Z. Plant Cell 19, 74–83 (2007).
  60. Kumar, S.V. & Wigge, P.A. H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis. Cell 140, 136–147 (2010).
  61. Zilberman, D., Coleman-Derr, D., Ballinger, T. & Henikoff, S. Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 456, 125–129 (2008).
  62. Martin-Trillo, M. et al. EARLY IN SHORT DAYS 1 (ESD1) encodes ACTIN-RELATED PROTEIN 6 (AtARP6), a putative component of chromatin remodelling complexes that positively regulates FLC accumulation in Arabidopsis. Development 133, 1241–1252 (2006).
  63. Francis, K.E. et al. Pollen tetrad-based visual assay for meiotic recombination in Arabidopsis. Proc. Natl. Acad. Sci. USA 104, 3913–3918 (2007).
  64. Barth, S., Melchinger, A.E., Devezi-Savula, B. & Lübberstedt, T. A high-throughput system for genome-wide measurement of genetic recombination in Arabidopsis thaliana based on transgenic markers. Funct. Integr. Genomics 1, 200–206 (2000).
  65. Jones, G.H. & Franklin, F.C.H. Meiotic crossing-over: obligation and interference. Cell 126, 246–248 (2006).
  66. Melamed-Bessudo, C., Yehuda, E., Stuitje, A.R. & Levy, A.A. A new seed-based assay for meiotic recombination in Arabidopsis thaliana. Plant J. 43, 458–466 (2005).
  67. Bishop, D.K., Park, D., Xu, L. & Kleckner, N. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell 69, 439–456 (1992).
  68. Shinohara, A., Ogawa, H. & Ogawa, T. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69, 457–470 (1992).
  69. Sanchez-Moran, E., Santos, J.-L., Jones, G.H. & Franklin, F.C.H. ASY1 mediates AtDMC1-dependent interhomolog recombination during meiosis in Arabidopsis. Genes Dev. 21, 2220–2233 (2007).
  70. Copenhaver, G.P., Browne, W.E. & Preuss, D. Assaying genome-wide recombination and centromere functions with Arabidopsis tetrads. Proc. Natl. Acad. Sci. USA 95, 247–252 (1998).
  71. Sanchez-Moran, E., Armstrong, S.J., Santos, J.L., Franklin, F.C.H. & Jones, G.H. Variation in chiasma frequency among eight accessions of Arabidopsis thaliana. Genetics 162, 1415–1422 (2002).
  72. Francis, R.A. et al. Characterizing the performance of the Conway-Maxwell Poisson generalized linear model. Risk Anal. 32, 167–183 (2012).
  73. Jackson, N. et al. Reduced meiotic crossovers and delayed prophase I progression in AtMLH3-deficient Arabidopsis. EMBO J. 25, 1315–1323 (2006).
  74. Blat, Y., Protacio, R.U., Hunter, N. & Kleckner, N. Physical and functional interactions among basic chromosome organizational features govern early steps of meiotic chiasma formation. Cell 111, 791–802 (2002).
  75. Panizza, S. et al. Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell 146, 372–383 (2011).
  76. Gerton, J.L. et al. Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97, 11383–11390 (2000).
  77. Morillo-Huesca, M., Clemente-Ruiz, M., Andújar, E. & Prado, F. The SWR1 histone replacement complex causes genetic instability and genome-wide transcription misregulation in the absence of H2A.Z. PLoS ONE 5, e12143 (2010).
  78. Papamichos-Chronakis, M., Watanabe, S., Rando, O.J. & Peterson, C.L. Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity. Cell 144, 200–213 (2011).
  79. Iacovoni, J.S. et al. High-resolution profiling of γH2AX around DNA double strand breaks in the mammalian genome. EMBO J. 29, 1446–1457 (2010).
  80. Savic, V. et al. Formation of dynamic γ-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Mol. Cell 34, 298–310 (2009).
  81. Meier, A. et al. Spreading of mammalian DNA-damage response factors studied by ChIP-chip at damaged telomeres. EMBO J. 26, 2707–2718 (2007).
  82. Kleckner, N. Chiasma formation: chromatin/axis interplay and the role(s) of the synaptonemal complex. Chromosoma 115, 175–194 (2006).
  83. Oliver, P.L. et al. Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa. PLoS Genet. 5, e1000753 (2009).
  84. Wu, Y., Close, T.J. & Lonardi, S. On the accurate construction of consensus genetic maps. Comput. Syst. Bioinformatics Conf. 7, 285–296 (2008).
  85. Borevitz, J.O. et al. Genome-wide patterns of single-feature polymorphism in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 104, 12057–12062 (2007).
  86. Clark, R.M. et al. Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana. Science 317, 338–342 (2007).
  87. Benson, G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 27, 573–580 (1999).
  88. Warburton, P.E., Giordano, J., Cheung, F., Gelfand, Y. & Benson, G. Inverted repeat structure of the human genome: the X-chromosome contains a preponderance of large, highly homologous inverted repeats that contain testes genes. Genome Res. 14, 1861–1869 (2004).
  89. Auton, A. & McVean, G. Recombination rate estimation in the presence of hotspots. Genome Res. 17, 1219–1227 (2007).
  90. Achim, Z. & Grothendieck, G. zoo: S3 infrastructure for regular and irregular time series. J. Stat. Softw. 14, 1–27 (2005).
  91. Berchowitz, L.E. & Copenhaver, G.P. Fluorescent Arabidopsis tetrads: a visual assay for quickly developing large crossover and crossover interference data sets. Nat. Protoc. 3, 41–50 (2008).
  92. Gan, X. et al. Multiple reference genomes and transcriptomes for Arabidopsis thaliana. Nature 477, 419–423 (2011).
  93. Arends, D., Prins, P., Jansen, R.C. & Broman, K.W. R/qtl: high-throughput multiple QTL mapping. Bioinformatics 26, 2990–2992 (2010).
  94. Higgins, J.D., Armstrong, S.J., Franklin, F.C.H. & Jones, G.H. The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis. Genes Dev. 18, 2557–2570 (2004).
  95. Ferdous, M. et al. Inter-homolog crossing-over and synapsis in Arabidopsis meiosis are dependent on the chromosome axis protein AtASY3. PLoS Genet. 8, e1002507 (2012).

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Author information

  1. These authors contributed equally to this work.

    • Kyuha Choi &
    • Xiaohui Zhao

Affiliations

  1. Department of Plant Sciences, University of Cambridge, Cambridge, UK.

    • Kyuha Choi,
    • Xiaohui Zhao,
    • Krystyna A Kelly,
    • Nataliya E Yelina,
    • Thomas J Hardcastle,
    • Piotr A Ziolkowski &
    • Ian R Henderson

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Oliver Venn &
    • Gil McVean

  3. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.

    • James D Higgins &
    • F Chris H Franklin

  4. Department of Biotechnology, Adam Mickiewicz University, Poznan, Poland.

    • Piotr A Ziolkowski

  5. Department of Biology and the Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • Gregory P Copenhaver

  6. Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

    • Gregory P Copenhaver

Contributions

K.C., J.D.H., N.E.Y. and P.A.Z. performed experiments. K.C., J.D.H., N.E.Y., P.A.Z., G.P.C., F.C.H.F. and I.R.H. designed experiments. X.Z., K.A.K., O.V., T.J.H., G.M. and I.R.H. designed and performed computational and statistical analyses. K.C., X.Z., K.A.K., O.V., J.D.H., N.E.Y., T.J.H., P.A.Z., G.P.C., F.C.H.F., G.M. and I.R.H. wrote the paper.

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The authors declare no competing financial interests.

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