Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin

Autoři: Yuh Chwen G. Lee aff001;  Yuki Ogiyama aff002;  Nuno M. C. Martins aff003;  Brian J. Beliveau aff004;  David Acevedo aff001;  C.-ting Wu aff003;  Giacomo Cavalli aff002;  Gary H. Karpen aff001
Působiště autorů: Department of Molecular and Cell Biology, UC Berkeley and BSE Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America aff001;  Institute of Human Genetics, CNRS, Montpellier, France aff002;  Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America aff003;  Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America aff004
Vyšlo v časopise: Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008673
Kategorie: Research Article


Membraneless pericentromeric heterochromatin (PCH) domains play vital roles in chromosome dynamics and genome stability. However, our current understanding of 3D genome organization does not include PCH domains because of technical challenges associated with repetitive sequences enriched in PCH genomic regions. We investigated the 3D architecture of Drosophila melanogaster PCH domains and their spatial associations with the euchromatic genome by developing a novel analysis method that incorporates genome-wide Hi-C reads originating from PCH DNA. Combined with cytogenetic analysis, we reveal a hierarchical organization of the PCH domains into distinct “territories.” Strikingly, H3K9me2-enriched regions embedded in the euchromatic genome show prevalent 3D interactions with the PCH domain. These spatial contacts require H3K9me2 enrichment, are likely mediated by liquid-liquid phase separation, and may influence organismal fitness. Our findings have important implications for how PCH architecture influences the function and evolution of both repetitive heterochromatin and the gene-rich euchromatin.

Klíčová slova:

Drosophila melanogaster – Embryos – Fluorescent in situ hybridization – Heterochromatin – Chromosome pairs – Invertebrate genomics – Islands – Euchromatin


1. Misteli T, Soutoglou E. The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat Rev Mol Cell Biol. 2009;10: 243–254. doi: 10.1038/nrm2651 19277046

2. Bickmore WA, van Steensel B. Genome Architecture: Domain Organization of Interphase Chromosomes. Cell. 2013;152: 1270–1284. doi: 10.1016/j.cell.2013.02.001 23498936

3. Sexton T, Cavalli G. The Role of Chromosome Domains in Shaping the Functional Genome. Cell. 2015;160: 1049–1059. doi: 10.1016/j.cell.2015.02.040 25768903

4. Bonev B, Cavalli G. Organization and function of the 3D genome. Nat Rev Genet. 2016;17: 661–678. doi: 10.1038/nrg.2016.112 27739532

5. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing Chromosome Conformation. Science. 2002;295: 1306–1311. doi: 10.1126/science.1067799 11847345

6. Lieberman-Aiden E, Berkum NL van, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome. Science. 2009;326: 289–293. doi: 10.1126/science.1181369 19815776

7. Denker A, Laat W de. The second decade of 3C technologies: detailed insights into nuclear organization. Genes Dev. 2016;30: 1357–1382. doi: 10.1101/gad.281964.116 27340173

8. Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M, et al. Three-Dimensional Folding and Functional Organization Principles of the Drosophila Genome. Cell. 2012;148: 458–472. doi: 10.1016/j.cell.2012.01.010 22265598

9. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012 [cited 11 Apr 2012]. doi: 10.1038/nature11082 22495300

10. Stadler MR, Haines JE, Eisen MB. Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo. In: eLife [Internet]. 17 Nov 2017 [cited 7 Sep 2018]. doi: 10.7554/eLife.29550 29148971

11. Arabidopsis Genome Initiative. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature. 2000;408: 796–815. doi: 10.1038/35048692 11130711

12. Smith CD, Shu S, Mungall CJ, Karpen GH. The Release 5.1 Annotation of Drosophila melanogaster Heterochromatin. Science. 2007;316: 1586–1591. doi: 10.1126/science.1139815 17569856

13. Karpen GH, Le M-H, Le H. Centric Heterochromatin and the Efficiency of Achiasmate Disjunction in Drosophila Female Meiosis. Science. 1996;273: 118–122. doi: 10.1126/science.273.5271.118 8658180

14. Dernburg AF, Sedat JW, Hawley RS. Direct evidence of a role for heterochromatin in meiotic chromosome segregation. Cell. 1996;86: 135–146. doi: 10.1016/s0092-8674(00)80084-7 8689681

15. Peters AHFM, O’Carroll D, Scherthan H, Mechtler K, Sauer S, Schöfer C, et al. Loss of the Suv39h Histone Methyltransferases Impairs Mammalian Heterochromatin and Genome Stability. Cell. 2001;107: 323–337. doi: 10.1016/s0092-8674(01)00542-6 11701123

16. Peng JC, Karpen GH. Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation. PLOS Genet. 2009;5: e1000435. doi: 10.1371/journal.pgen.1000435 19325889

17. Janssen A, Colmenares SU, Karpen GH. Heterochromatin: Guardian of the Genome. Annu Rev Cell Dev Biol. 2018;34: 265–288. doi: 10.1146/annurev-cellbio-100617-062653 30044650

18. James TC, Elgin SC. Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol Cell Biol. 1986;6: 3862–3872. doi: 10.1128/mcb.6.11.3862 3099166

19. Jacobs SA, Taverna SD, Zhang Y, Briggs SD, Li J, Eissenberg JC, et al. Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. EMBO J. 2001;20: 5232–5241. doi: 10.1093/emboj/20.18.5232 11566886

20. Zhang P, Spradling AC. The Drosophila Salivary Gland Chromocenter Contains Highly Polytenized Subdomains of Mitotic Heterochromatin. Genetics. 1995;139: 659–670. 7713423

21. Mayer R, Brero A, von Hase J, Schroeder T, Cremer T, Dietzel S. Common themes and cell type specific variations of higher order chromatin arrangements in the mouse. BMC Cell Biol. 2005;6: 44. doi: 10.1186/1471-2121-6-44 16336643

22. Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017;547: 236–240. doi: 10.1038/nature22822 28636604

23. Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X, Karpen GH. Phase separation drives heterochromatin domain formation. Nature. 2017;547: 241–245. doi: 10.1038/nature22989 28636597

24. Wakimoto BT, Hearn MG. The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster. Genetics. 1990;125: 141–154. 2111264

25. Gowen JW, Gay EH. EFFECT OF TEMPERATURE ON EVERSPORTING EYE COLOR IN DROSOPHILA MELANOGASTER. Science. 1933;77: 312. doi: 10.1126/science.77.1995.312 17820329

26. Girton JR, Johansen KM. Chromatin structure and the regulation of gene expression: the lessons of PEV in Drosophila. Adv Genet. 2008;61: 1–43. doi: 10.1016/S0065-2660(07)00001-6 18282501

27. Elgin SCR, Reuter G. Position-effect variegation, heterochromatin formation, and gene silencing in Drosophila. Cold Spring Harb Perspect Biol. 2013;5: a017780. doi: 10.1101/cshperspect.a017780 23906716

28. Falk M, Feodorova Y, Naumova N, Imakaev M, Lajoie BR, Leonhardt H, et al. Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature. 2019;570: 395. doi: 10.1038/s41586-019-1275-3 31168090

29. Vogel MJ, Guelen L, de Wit E, Hupkes DP, Lodén M, Talhout W, et al. Human heterochromatin proteins form large domains containing KRAB-ZNF genes. Genome Res. 2006;16: 1493–1504. doi: 10.1101/gr.5391806 17038565

30. Wen B, Wu H, Shinkai Y, Irizarry RA, Feinberg AP. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells. Nat Genet. 2009;41: 246–250. doi: 10.1038/ng.297 19151716

31. Riddle NC, Minoda A, Kharchenko PV, Alekseyenko AA, Schwartz YB, Tolstorukov MY, et al. Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res. 2011;21: 147–163. doi: 10.1101/gr.110098.110 21177972

32. Dernburg AF, Broman KW, Fung JC, Marshall WF, Philips J, Agard DA, et al. Perturbation of Nuclear Architecture by Long-Distance Chromosome Interactions. Cell. 1996;85: 745–759. doi: 10.1016/s0092-8674(00)81240-4 8646782

33. Csink AK, Henikoff S. Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature. 1996;381: 529–531. doi: 10.1038/381529a0 8632827

34. Lee YCG. The Role of piRNA-Mediated Epigenetic Silencing in the Population Dynamics of Transposable Elements in Drosophila melanogaster. PLoS Genet. 2015;11: e1005269. doi: 10.1371/journal.pgen.1005269 26042931

35. Lee YCG, Karpen GH. Pervasive epigenetic effects of Drosophila euchromatic transposable elements impact their evolution. eLife. 2017;6. doi: 10.7554/eLife.25762 28695823

36. Hoskins RA, Carlson JW, Kennedy C, Acevedo D, Evans-Holm M, Frise E, et al. Sequence Finishing and Mapping of Drosophila melanogaster Heterochromatin. Science. 2007;316: 1625–1628. doi: 10.1126/science.1139816 17569867

37. Hoskins RA, Carlson JW, Wan KH, Park S, Mendez I, Galle SE, et al. The Release 6 reference sequence of the Drosophila melanogaster genome. Genome Res. 2015; gr.185579.114. doi: 10.1101/gr.185579.114 25589440

38. Schuettengruber B, Oded Elkayam N, Sexton T, Entrevan M, Stern S, Thomas A, et al. Cooperativity, specificity, and evolutionary stability of Polycomb targeting in Drosophila. Cell Rep. 2014;9: 219–233. doi: 10.1016/j.celrep.2014.08.072 25284790

39. Gatti M, Pimpinelli S. Functional Elements in Drosophila Melanogaster Heterochromatin. Annu Rev Genet. 1992;26: 239–276. doi: 10.1146/ 1482113

40. Derrien T, Estellé J, Sola SM, Knowles DG, Raineri E, Guigó R, et al. Fast Computation and Applications of Genome Mappability. PLOS ONE. 2012;7: e30377. doi: 10.1371/journal.pone.0030377 22276185

41. Dernburg AF. In Situ Hybridization to Somatic Chromosomes in Drosophila. Cold Spring Harb Protoc. 2011;2011: pdb.top065540. doi: 10.1101/pdb.top065540 21880819

42. Filion GJ, van Bemmel JG, Braunschweig U, Talhout W, Kind J, Ward LD, et al. Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell. 2010;143: 212–224. doi: 10.1016/j.cell.2010.09.009 20888037

43. Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, et al. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature. 2011;471: 480–485. doi: 10.1038/nature09725 21179089

44. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, et al. The developmental transcriptome of Drosophila melanogaster. Nature. 2011;471: 473–479. doi: 10.1038/nature09715 21179090

45. Beliveau BJ, Joyce EF, Apostolopoulos N, Yilmaz F, Fonseka CY, McCole RB, et al. Versatile design and synthesis platform for visualizing genomes with Oligopaint FISH probes. Proc Natl Acad Sci U S A. 2012;109: 21301–21306. doi: 10.1073/pnas.1213818110 23236188

46. Beliveau BJ, Apostolopoulos N, Wu C. Visualizing genomes with Oligopaint FISH probes. Curr Protoc Mol Biol. 2014;105: Unit 14.23. doi: 10.1002/0471142727.mb1423s105 24510436

47. Beliveau BJ, Boettiger AN, Nir G, Bintu B, Yin P, Zhuang X, et al. In Situ Super-Resolution Imaging of Genomic DNA with OligoSTORM and OligoDNA-PAINT. In: Erfle H, editor. Super-Resolution Microscopy: Methods and Protocols. New York, NY: Springer New York; 2017. pp. 231–252. doi: 10.1007/978-1-4939-7265-4_19

48. Lohe AR, Brutlag DL. Multiplicity of satellite DNA sequences in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1986;83: 696–700. doi: 10.1073/pnas.83.3.696 3080746

49. Lohe AR, Hilliker AJ, Roberts PA. Mapping Simple Repeated DNA Sequences in Heterochromatin of Drosophila Melanogaster. Genetics. 1993;134: 1149–1174. 8375654

50. Rebollo R, Karimi MM, Bilenky M, Gagnier L, Miceli-Royer K, Zhang Y, et al. Retrotransposon-Induced Heterochromatin Spreading in the Mouse Revealed by Insertional Polymorphisms. PLoS Genet. 2011;7: e1002301. doi: 10.1371/journal.pgen.1002301 21980304

51. Sentmanat MF, Elgin SCR. Ectopic assembly of heterochromatin in Drosophila melanogaster triggered by transposable elements. Proc Natl Acad Sci. 2012;109: 14104–14109. doi: 10.1073/pnas.1207036109 22891327

52. Charlesworth B, Langley CH. The population genetics of Drosophila transposable elements. Annu Rev Genet. 1989;23: 251–287. doi: 10.1146/ 2559652

53. Cridland JM, Macdonald SJ, Long AD, Thornton KR. Abundance and Distribution of Transposable Elements in Two Drosophila QTL Mapping Resources. Mol Biol Evol. 2013;30: 2311–2327. doi: 10.1093/molbev/mst129 23883524

54. Kofler R, Nolte V, Schlötterer C. Tempo and Mode of Transposable Element Activity in Drosophila. PLoS Genet. 2015;11: e1005406. doi: 10.1371/journal.pgen.1005406 26186437

55. Park PJ. ChIP–seq: advantages and challenges of a maturing technology. Nat Rev Genet. 2009;10: 669–680. doi: 10.1038/nrg2641 19736561

56. Nakato R, Shirahige K. Recent advances in ChIP-seq analysis: from quality management to whole-genome annotation. Brief Bioinform. 2017;18: 279–290. doi: 10.1093/bib/bbw023 26979602

57. Ribbeck K, Görlich D. The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion. EMBO J. 2002;21: 2664–2671. doi: 10.1093/emboj/21.11.2664 12032079

58. Lee YCG, Langley CH. Transposable elements in natural populations of Drosophila melanogaster. Philos Trans R Soc B Biol Sci. 2010;365: 1219–1228. doi: 10.1098/rstb.2009.0318 20308097

59. Barrón MG, Fiston-Lavier A-S, Petrov DA, González J. Population Genomics of Transposable Elements in Drosophila. Annu Rev Genet. 2014;48: 561–581. doi: 10.1146/annurev-genet-120213-092359 25292358

60. Lack JB, Cardeno CM, Crepeau MW, Taylor W, Corbett-Detig RB, Stevens KA, et al. The Drosophila Genome Nexus: A Population Genomic Resource of 623 Drosophila melanogaster Genomes, Including 197 from a Single Ancestral Range Population. Genetics. 2015; genetics.115.174664. doi: 10.1534/genetics.115.174664 25631317

61. Petrov DA, Fiston-Lavier A-S, Lipatov M, Lenkov K, González J. Population genomics of transposable elements in Drosophila melanogaster. Mol Biol Evol. 2011;28: 1633–1644. doi: 10.1093/molbev/msq337 21172826

62. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409: 860–921. doi: 10.1038/35057062 11237011

63. Lichter P, Cremer T, Borden J, Manuelidis L, Ward DC. Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet. 1988;80: 224–234. doi: 10.1007/bf01790090 3192212

64. Pinkel D, Landegent J, Collins C, Fuscoe J, Segraves R, Lucas J, et al. Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci U S A. 1988;85: 9138–9142. doi: 10.1073/pnas.85.23.9138 2973607

65. Kalhor R, Tjong H, Jayathilaka N, Alber F, Chen L. Genome architectures revealed by tethered chromosome conformation capture and population-based modeling. Nat Biotechnol. 2012;30: 90–98. doi: 10.1038/nbt.2057 22198700

66. Williamson I, Berlivet S, Eskeland R, Boyle S, Illingworth RS, Paquette D, et al. Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev. 2014;28: 2778–2791. doi: 10.1101/gad.251694.114 25512564

67. Rosin LF, Nguyen SC, Joyce EF. Condensin II drives large-scale folding and spatial partitioning of interphase chromosomes in Drosophila nuclei. PLOS Genet. 2018;14: e1007393. doi: 10.1371/journal.pgen.1007393 30001329

68. Dekker J, Marti-Renom MA, Mirny LA. Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nat Rev Genet. 2013;14: 390–403. doi: 10.1038/nrg3454 23657480

69. Haddad N, Jost D, Vaillant C. Perspectives: using polymer modeling to understand the formation and function of nuclear compartments. Chromosome Res. 2017;25: 35–50. doi: 10.1007/s10577-016-9548-2 28091870

70. Monahan K, Horta A, Lomvardas S. LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice. Nature. 2019; 1. doi: 10.1038/s41586-018-0845-0 30626972

71. Swenson JM, Colmenares SU, Strom AR, Costes SV, Karpen GH. The composition and organization of Drosophila heterochromatin are heterogeneous and dynamic. eLife. 2016;5: e16096. doi: 10.7554/eLife.16096 27514026

72. Haynes KA, Gracheva E, Elgin SCR. A Distinct Type of Heterochromatin Within Drosophila melanogaster Chromosome 4. Genetics. 2007;175: 1539–1542. doi: 10.1534/genetics.106.066407 17194780

73. Phalke S, Nickel O, Walluscheck D, Hortig F, Onorati MC, Reuter G. Retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine-5 methyltransferase DNMT2. Nat Genet. 2009;41: 696–702. doi: 10.1038/ng.360 19412177

74. Seum C, Reo E, Peng H, Iii FJR, Spierer P, Bontron S. Drosophila SETDB1 Is Required for Chromosome 4 Silencing. PLOS Genet. 2007;3: e76. doi: 10.1371/journal.pgen.0030076 17500594

75. Hearn MG, Hedrick A, Grigliatti TA, Wakimoto BT. The effect of modifiers of position-effect variegation on the variegation of heterochromatic genes of Drosophila melanogaster. Genetics. 1991;128: 785–797. 1916244

76. Yasuhara JC, Wakimoto BT. Molecular Landscape of Modified Histones in Drosophila Heterochromatic Genes and Euchromatin-Heterochromatin Transition Zones. PLoS Genet. 2008;4: e16. doi: 10.1371/journal.pgen.0040016 18208336

77. Piacentini L, Fanti L, Berloco M, Perrini B, Pimpinelli S. Heterochromatin protein 1 (HP1) is associated with induced gene expression in Drosophila euchromatin. J Cell Biol. 2003;161: 707–714. doi: 10.1083/jcb.200303012 12756231

78. Piacentini L, Fanti L, Negri R, Vescovo VD, Fatica A, Altieri F, et al. Heterochromatin Protein 1 (HP1a) Positively Regulates Euchromatic Gene Expression through RNA Transcript Association and Interaction with hnRNPs in Drosophila. PLOS Genet. 2009;5: e1000670. doi: 10.1371/journal.pgen.1000670 19798443

79. Cryderman DE, Grade SK, Li Y, Fanti L, Pimpinelli S, Wallrath LL. Role of Drosophila HP1 in euchromatic gene expression. Dev Dyn. 2005;232: 767–774. doi: 10.1002/dvdy.20310 15704177

80. Joyce EF, Erceg J, Wu C -ting. Pairing and anti-pairing: a balancing act in the diploid genome. Curr Opin Genet Dev. 2016;37: 119–128. doi: 10.1016/j.gde.2016.03.002 27065367

81. Henikoff S, Dreesen TD. Trans-inactivation of the Drosophila brown gene: evidence for transcriptional repression and somatic pairing dependence. Proc Natl Acad Sci. 1989;86: 6704–6708. doi: 10.1073/pnas.86.17.6704 2505257

82. Elliott TA, Gregory TR. Do larger genomes contain more diverse transposable elements? BMC Evol Biol. 2015;15: 69. doi: 10.1186/s12862-015-0339-8 25896861

83. Consortium IHGS. Finishing the euchromatic sequence of the human genome. Nature. 2004;431: 931–945. doi: 10.1038/nature03001 15496913

84. Stewart C, Kural D, Strömberg MP, Walker JA, Konkel MK, Stütz AM, et al. A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans. PLoS Genet. 2011;7: e1002236. doi: 10.1371/journal.pgen.1002236 21876680

85. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. An integrated map of structural variation in 2,504 human genomes. Nature. 2015;526: 75–81. doi: 10.1038/nature15394 26432246

86. Dolgin ES, Charlesworth B, Cutter AD. Population frequencies of transposable elements in selfing and outcrossing Caenorhabditis nematodes. Genet Res. 2008;90: 317–329. doi: 10.1017/S0016672308009440 18840306

87. Laricchia KM, Zdraljevic S, Cook DE, Andersen EC. Natural Variation in the Distribution and Abundance of Transposable Elements Across the Caenorhabditis elegans Species. Mol Biol Evol. 2017;34: 2187–2202. doi: 10.1093/molbev/msx155 28486636

88. Rahman R, Chirn G, Kanodia A, Sytnikova YA, Brembs B, Bergman CM, et al. Unique transposon landscapes are pervasive across Drosophila melanogaster genomes. Nucleic Acids Res. 2015;43: 10655–10672. doi: 10.1093/nar/gkv1193 26578579

89. Wright SI, Le QH, Schoen DJ, Bureau TE. Population dynamics of an Ac-like transposable element in self- and cross-pollinating arabidopsis. Genetics. 2001;158: 1279–1288. 11454774

90. Quadrana L, Silveira AB, Mayhew GF, LeBlanc C, Martienssen RA, Jeddeloh JA, et al. The Arabidopsis thaliana mobilome and its impact at the species level. eLife. 2016;5: e15716. doi: 10.7554/eLife.15716 27258693

91. Stuart T, Eichten SR, Cahn J, Karpievitch YV, Borevitz JO, Lister R. Population scale mapping of transposable element diversity reveals links to gene regulation and epigenomic variation. eLife. 2016;5: e20777. doi: 10.7554/eLife.20777 27911260

92. Mackay TFC, Richards S, Stone EA, Barbadilla A, Ayroles JF, Zhu D, et al. The Drosophila melanogaster Genetic Reference Panel. Nature. 2012;482: 173–178. doi: 10.1038/nature10811 22318601

93. Babraham Bioinformatics—Trim Galore! [cited 18 Nov 2016]. Available:

94. Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinforma Oxf Engl. 2011;27: 2987–2993. doi: 10.1093/bioinformatics/btr509 21903627

95. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based Analysis of ChIP-Seq (MACS). Genome Biol. 2008;9: R137. doi: 10.1186/gb-2008-9-9-r137 18798982

96. Li Q, Brown JB, Huang H, Bickel PJ. Measuring reproducibility of high-throughput experiments. Ann Appl Stat. 2011;5: 1752–1779. doi: 10.1214/11-AOAS466

97. Kaminker JS, Bergman CM, Kronmiller B, Carlson J, Svirskas R, Patel S, et al. The transposable elements of the Drosophila melanogaster euchromatin: a genomics perspective. Genome Biol. 2002;3: RESEARCH0084.

98. Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010;26: 589–595. doi: 10.1093/bioinformatics/btp698 20080505

99. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38: 576–589. doi: 10.1016/j.molcel.2010.05.004 20513432

100. Williams BR, Bateman JR, Novikov ND, Wu C-T. Disruption of Topoisomerase II Perturbs Pairing in Drosophila Cell Culture. Genetics. 2007;177: 31–46. doi: 10.1534/genetics.107.076356 17890361

101. Beliveau BJ, Kishi JY, Nir G, Sasaki HM, Saka SK, Nguyen SC, et al. OligoMiner provides a rapid, flexible environment for the design of genome-scale oligonucleotide in situ hybridization probes. Proc Natl Acad Sci U S A. 2018;115: E2183–E2192. doi: 10.1073/pnas.1714530115 29463736

102. Nir G, Farabella I, Estrada CP, Ebeling CG, Beliveau BJ, Sasaki HM, et al. Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling. PLOS Genet. 2018;14: e1007872. doi: 10.1371/journal.pgen.1007872 30586358

103. Rand MD. A method of permeabilization of Drosophila embryos for assays of small molecule activity. J Vis Exp JoVE. 2014. doi: 10.3791/51634 25046169

104. Rand MD, Kearney AL, Dao J, Clason T. Permeabilization of Drosophila embryos for introduction of small molecules. Insect Biochem Mol Biol. 2010;40: 792–804. doi: 10.1016/j.ibmb.2010.07.007 20727969

105. Erceg J, AlHaj Abed J, Goloborodko A, Lajoie BR, Fudenberg G, Abdennur N, et al. The genome-wide multi-layered architecture of chromosome pairing in early Drosophila embryos. Nat Commun. 2019;10: 4486. doi: 10.1038/s41467-019-12211-8 31582744

106. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9: 676–682. doi: 10.1038/nmeth.2019 22743772

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 3
Nejčtenější tento týden
Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se