1932

Abstract

The modENCODE (Model Organism Encyclopedia of DNA Elements) Consortium aimed to map functional elements—including transcripts, chromatin marks, regulatory factor binding sites, and origins of DNA replication—in the model organisms and . During its five-year span, the consortium conducted more than 2,000 genome-wide assays in developmentally staged animals, dissected tissues, and homogeneous cell lines. Analysis of these data sets provided foundational insights into genome, epigenome, and transcriptome structure and the evolutionary turnover of regulatory pathways. These studies facilitated a comparative analysis with similar data types produced by the ENCODE Consortium for human cells. Genome organization differs drastically in these distant species, and yet quantitative relationships among chromatin state, transcription, and cotranscriptional RNA processing are deeply conserved. Of the many biological discoveries of the modENCODE Consortium, we highlight insights that emerged from integrative studies. We focus on operational and scientific lessons that may aid future projects of similar scale or aims in other, emerging model systems.

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2015-08-24
2024-10-14
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Literature Cited

  1. Allen MA, Hillier LW, Waterston RH, Blumenthal T. 1.  2011. A global analysis of C. elegans trans-splicing. Genome Res. 21:255–64 [Google Scholar]
  2. Araya CL, Kawli T, Kundaje A, Jiang L, Wu B. 2.  et al. 2014. Regulatory analysis of the C. elegans genome with spatiotemporal resolution. Nature 512:400–5 [Google Scholar]
  3. Arnold CD, Gerlach D, Stelzer C, Boryn LM, Rath M, Stark A. 3.  2013. Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339:1074–77 [Google Scholar]
  4. Babiarz JE, Hsu R, Melton C, Thomas M, Ullian EM, Blelloch R. 4.  2011. A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing. RNA 17:1489–501 [Google Scholar]
  5. Baillie JK, Barnett MW, Upton KR, Gerhardt DJ, Richmond TA. 5.  et al. 2011. Somatic retrotransposition alters the genetic landscape of the human brain. Nature 479:534–37 [Google Scholar]
  6. Bank EM, Gruenbaum Y. 6.  2011. The nuclear lamina and heterochromatin: a complex relationship. Biochem. Soc. Trans. 39:1705–9 [Google Scholar]
  7. Berezikov E, Liu N, Flynt AS, Hodges E, Rooks M. 7.  et al. 2010. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nat. Genet. 42:6–9; author reply, 9–10 [Google Scholar]
  8. Berezikov E, Robine N, Samsonova A, Westholm JO, Naqvi A. 8.  et al. 2011. Deep annotation of Drosophila melanogaster microRNAs yields insights into their processing, modification, and emergence. Genome Res. 21:203–15 [Google Scholar]
  9. Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M. 9.  2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74 [Google Scholar]
  10. Biggin MD. 10.  2011. Animal transcription networks as highly connected, quantitative continua. Dev. Cell 21:611–26 [Google Scholar]
  11. Billi AC, Freeberg MA, Day AM, Chun SY, Khivansara V, Kim JK. 11.  2013. A conserved upstream motif orchestrates autonomous, germline-enriched expression of Caenorhabditis elegans piRNAs. PLOS Genet. 9:e1003392 [Google Scholar]
  12. Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR. 12.  et al. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816 [Google Scholar]
  13. Boley N, Stoiber MH, Booth BW, Wan K, Hoskins RA. 13.  et al. 2014. Genome guided transcript construction from integrative analysis of RNA sequence data. Nat. Biotechnol. 32:341–46 [Google Scholar]
  14. Boyle AP, Araya CL, Brdlik C, Cayting P, Cheng C. 14.  et al. 2014. Comparative analysis of regulatory information and circuits across distant species. Nature 512:453–56 [Google Scholar]
  15. Braunschweig U, Gueroussov S, Plocik AM, Graveley BR, Blencowe BJ. 15.  2013. Dynamic integration of splicing within gene regulatory pathways. Cell 152:1252–69 [Google Scholar]
  16. Brooks AN, Yang L, Duff MO, Hansen KD, Park JW. 16.  et al. 2010. Conservation of an RNA regulatory map between Drosophila and mammals. Genome Res. 21:193–202 [Google Scholar]
  17. Brown JB, Boley N, Eisman R, May GE, Stoiber MH. 17.  et al. 2014. Diversity and dynamics of the Drosophila transcriptome. Nature 512:393–99 [Google Scholar]
  18. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. 18.  2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10:1213–18 [Google Scholar]
  19. Celniker SE, Dillon LAL, Gerstein MB, Gunsalus KC, Henikoff S. 19.  et al. 2009. Unlocking the secrets of the genome. Nature 459:927–30 [Google Scholar]
  20. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O. 20.  et al. 2011. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–69 [Google Scholar]
  21. Chen J, Miller A, Kirchmaier AL, Irudayaraj JM. 21.  2012. Single-molecule tools elucidate H2A.Z nucleosome composition. J. Cell Sci. 125:2954–64 [Google Scholar]
  22. Chen RA, Down TA, Stempor P, Chen QB, Egelhofer TA. 22.  et al. 2013. The landscape of RNA polymerase II transcription initiation in C. elegans reveals promoter and enhancer architectures. Genome Res. 23:1339–37 [Google Scholar]
  23. Chen RA, Stempor P, Down TA, Zeiser E, Feuer SK, Ahringer J. 23.  2014. Extreme HOT regions are CpG-dense promoters in C. elegans and humans. Genome Res. 24:1138–46 [Google Scholar]
  24. Chen Y, Negre N, Li Q, Mieczkowska JO, Slattery M. 24.  et al. 2012. Systematic evaluation of factors influencing ChIP-seq fidelity. Nat. Methods 9:609–14 [Google Scholar]
  25. Chen Z-X, Sturgill D, Qu C, Jiang H, Park S. 25.  et al. 2014. Comparative validation of the D. melanogaster modENCODE transcriptome annotation. Genome Res. 24:1209–23 [Google Scholar]
  26. Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S. 26.  et al. 2005. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308:1149–54 [Google Scholar]
  27. Cherbas L, Willingham A, Zhang D, Yang L, Zou Y. 27.  et al. 2011. The transcriptional diversity of 25 Drosophila cell lines. Genome Res. 21:301–14 [Google Scholar]
  28. Curtis HJ, Sibley CR, Wood MJ. 28.  2012. Mirtrons, an emerging class of atypical miRNA. Wiley Interdiscip. Rev. RNA 3:617–32 [Google Scholar]
  29. Darnell RB. 29.  2011. HITS-CLIP: panoramic views of protein-RNA regulation in living cells. Wiley Interdiscip. Rev. RNA 1:266–86 [Google Scholar]
  30. de Almeida SF, Grosso AR, Koch F, Fenouil R, Carvalho S. 30.  et al. 2011. Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36. Nat. Struct. Mol. Biol. 18:977–83 [Google Scholar]
  31. de Wit E, Braunschweig U, Greil F, Bussemaker HJ, van Steensel B. 31.  2008. Global chromatin domain organization of the Drosophila genome. PLOS Genet. 4:e1000045 [Google Scholar]
  32. de Wit E, de Laat W. 32.  2012. A decade of 3C technologies: insights into nuclear organization. Genes Dev. 26:11–24 [Google Scholar]
  33. Deal RB, Henikoff JG, Henikoff S. 33.  2010. Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science 328:1161–64 [Google Scholar]
  34. Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA. 34.  et al. 2013. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503:371–76 [Google Scholar]
  35. Ding Q, MacAlpine DM. 35.  2010. Preferential re-replication of Drosophila heterochromatin in the absence of geminin. PLOS Genet. 6:e1001112 [Google Scholar]
  36. Dinger ME, Amaral PP, Mercer TR, Pang KC, Bruce SJ. 36.  et al. 2008. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res. 18:1433–45 [Google Scholar]
  37. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T. 37.  et al. 2012. Landscape of transcription in human cells. Nature 489:101–8 [Google Scholar]
  38. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C. 38.  et al. 2013. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21 [Google Scholar]
  39. Dodd IB, Micheelsen MA, Sneppen K, Thon G. 39.  2007. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129:813–22 [Google Scholar]
  40. Dong X, Greven MC, Kundaje A, Djebali S, Brown JB. 40.  et al. 2012. Modeling gene expression using chromatin features in various cellular contexts. Genome Biol. 13:R53 [Google Scholar]
  41. Dorn R, Reuter G, Loewendorf A. 41.  2001. Transgene analysis proves mRNA trans-splicing at the complex mod(mdg4) locus in. Drosophila. PNAS 98:9724–29 [Google Scholar]
  42. Eaton ML, Prinz JA, MacAlpine HK, Tretyakov G, Kharchenko PV, MacAlpine DM. 42.  2011. Chromatin signatures of the Drosophila replication program. Genome Res. 21:164–74 [Google Scholar]
  43. Egelhofer TA, Minoda A, Klugman S, Lee K, Kolasinska-Zwierz P. 43.  et al. 2011. An assessment of histone-modification antibody quality. Nat. Struct. Mol. Biol. 18:91–93 [Google Scholar]
  44. Engreitz JM, Sirokman K, McDonel P, Shishkin AA, Surka C. 44.  et al. 2014. RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159:188–99 [Google Scholar]
  45. Engstrom PG, Suzuki H, Ninomiya N, Akalin A, Sessa L. 45.  et al. 2006. Complex loci in human and mouse genomes. PLOS Genet. 2:e47 [Google Scholar]
  46. Ernst J, Kellis M. 46.  2010. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat. Biotechnol. 28:817–25 [Google Scholar]
  47. Fatica A, Bozzoni I. 47.  2014. Long non-coding RNAs: new players in cell differentiation and development. Nat. Rev. Genet. 15:7–21 [Google Scholar]
  48. Findlay GD, MacCoss MJ, Swanson WJ. 48.  2009. Proteomic discovery of previously unannotated, rapidly evolving seminal fluid genes in Drosophila. Genome Res. 19:886–96 [Google Scholar]
  49. Fisher WW, Li JJ, Hammonds AS, Brown JB, Pfeiffer BD. 49.  et al. 2012. DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila. PNAS 109:21330–35 [Google Scholar]
  50. Frise E, Hammonds AS, Celniker SE. 50.  2010. Systematic image-driven analysis of the spatial Drosophila embryonic expression landscape. Mol. Syst. Biol. 6:345 [Google Scholar]
  51. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P. 51.  et al. 2014. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat. Neurosci. 17:667–69 [Google Scholar]
  52. Gent JI, Schvarzstein M, Villeneuve AM, Gu SG, Jantsch V. 52.  et al. 2009. A Caenorhabditis elegans RNA-directed RNA polymerase in sperm development and endogenous RNA interference. Genetics 183:1297–314 [Google Scholar]
  53. Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI. 53.  et al. 2010. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 330:1775–87 [Google Scholar]
  54. Gerstein MB, Rozowsky J, Yan KK, Wang D, Cheng C. 54.  et al. 2014. Comparative analysis of the transcriptome across distant species. Nature 512:445–48 [Google Scholar]
  55. Ghildiyal M, Seitz H, Horwich MD, Li C, Du T. 55.  et al. 2008. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320:1077–81 [Google Scholar]
  56. Gingeras TR. 56.  2009. Implications of chimaeric non-co-linear transcripts. Nature 461:206–11 [Google Scholar]
  57. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM. 57.  et al. 2011. The developmental transcriptome of Drosophila melanogaster. Nature 471:473–79 [Google Scholar]
  58. Gu SG, Pak J, Guang S, Maniar JM, Kennedy S, Fire A. 58.  2012. Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint. Nat. Genet. 44:157–64 [Google Scholar]
  59. Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK. 59.  et al. 2011. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477:295–300 [Google Scholar]
  60. Han T, Manoharan AP, Harkins TT, Bouffard P, Fitzpatrick C. 60.  et al. 2009. 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans. PNAS 106:18674–79 [Google Scholar]
  61. Heger P, Marin B, Schierenberg E. 61.  2009. Loss of the insulator protein CTCF during nematode evolution. BMC Mol. Biol. 10:84 [Google Scholar]
  62. Henikoff JG, Belsky JA, Krassovsky K, MacAlpine DM, Henikoff S. 62.  2011. Epigenome characterization at single base-pair resolution. PNAS 108:18318–23 [Google Scholar]
  63. Hilgers V, Lemke SB, Levine M. 63.  2012. ELAV mediates 3′ UTR extension in the Drosophila nervous system. Genes Dev. 26:2259–64 [Google Scholar]
  64. Hillier LW, Reinke V, Green P, Hirst M, Marra MA, Waterston RH. 64.  2009. Massively parallel sequencing of the polyadenylated transcriptome of C. elegans. Genome Res. 19:657–66 [Google Scholar]
  65. Ho JW, Jung YL, Liu T, Alver BH, Lee S. 65.  et al. 2014. Comparative analysis of metazoan chromatin organization. Nature 512:449–52 [Google Scholar]
  66. Horiuchi T, Giniger E, Aigaki T. 66.  2003. Alternative trans-splicing of constant and variable exons of a Drosophila axon guidance gene, lola. Genes Dev. 17:2496–501 [Google Scholar]
  67. Hoskins RA, Landolin JM, Brown JB, Sandler JE, Takahashi H. 67.  et al. 2011. Genome-wide analysis of promoter architecture in Drosophila melanogaster. Genome Res. 21:182–92 [Google Scholar]
  68. Huang S, Litt M, Felsenfeld G. 68.  2005. Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications. Genes Dev. 19:1885–93 [Google Scholar]
  69. Ikegami K, Egelhofer TA, Strome S, Lieb JD. 69.  2010. Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2. Genome Biol. 11:R120 [Google Scholar]
  70. Jacquier A. 70.  2009. The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat. Rev. Genet. 10:833–44 [Google Scholar]
  71. Jung YL, Luquette LJ, Ho JW, Ferrari F, Tolstorukov M. 71.  et al. 2014. Impact of sequencing depth in ChIP-seq experiments. Nucleic Acids Res. 42:e74 [Google Scholar]
  72. Kalinka AT, Varga KM, Gerrard DT, Preibisch S, Corcoran DL. 72.  et al. 2010. Gene expression divergence recapitulates the developmental hourglass model. Nature 468:811–14 [Google Scholar]
  73. Kasinathan S, Orsi GA, Zentner GE, Ahmad K, Henikoff S. 73.  2014. High-resolution mapping of transcription factor binding sites on native chromatin. Nat. Methods 11:203–9 [Google Scholar]
  74. Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC. 74.  et al. 2011. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 471:480–85 [Google Scholar]
  75. Kharchenko PV, Tolstorukov MY, Park PJ. 75.  2008. Design and analysis of ChIP-seq experiments for DNA-binding proteins. Nat. Biotechnol. 26:1351–59 [Google Scholar]
  76. Khare SP, Habib F, Sharma R, Gadewal N, Gupta S, Galande S. 76.  2011. HIstome—a relational knowledgebase of human histone proteins and histone modifying enzymes. Nucleic Acids Res. 40:D337–42 [Google Scholar]
  77. King FJ, Szakmary A, Cox DN, Lin H. 77.  2001. Yb modulates the divisions of both germline and somatic stem cells through piwi- and hh-mediated mechanisms in the Drosophila ovary. Mol. Cell 7:497–508 [Google Scholar]
  78. Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J. 78.  2009. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat. Genet. 41:376–81 [Google Scholar]
  79. Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A. 79.  et al. 2013. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231–35 [Google Scholar]
  80. Ladewig E, Okamura K, Flynt AS, Westholm JO, Lai EC. 80.  2012. Discovery of hundreds of mirtrons in mouse and human small RNA data. Genome Res. 22:1634–45 [Google Scholar]
  81. Landt SG, Marinov GK, Kundaje A, Kheradpour P, Pauli F. 81.  et al. 2012. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res. 22:1813–31 [Google Scholar]
  82. Lau NC, Robine N, Martin R, Chung WJ, Niki Y. 82.  et al. 2009. Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Res. 19:1776–85 [Google Scholar]
  83. Lee H, McManus CJ, Cho D-Y, Eaton ML, Renda F. 83.  et al. 2014. DNA copy number evolution in Drosophila cell lines. Genome Biol. 15:R70 [Google Scholar]
  84. Li H, Ruan J, Durbin R. 84.  2008. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 18:1851–58 [Google Scholar]
  85. Li JJ, Huang H, Bickel PJ, Brenner SE. 85.  2014. Comparison of D. melanogaster and C. elegans developmental stages, tissues, and cells by modENCODE RNA-seq data. Genome Res. 24:1086–101 [Google Scholar]
  86. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T. 86.  et al. 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–93 [Google Scholar]
  87. Liu T, Rechtsteiner A, Egelhofer TA, Vielle A, Latorre I. 87.  et al. 2011. Broad chromosomal domains of histone modification patterns in C. elegans. Genome Res. 21:227–36 [Google Scholar]
  88. Lubelsky Y, Prinz JA, DeNapoli L, Li Y, Belsky JA, MacAlpine DM. 88.  2014. DNA replication and transcription programs respond to the same chromatin cues. Genome Res. 24:1102–14 [Google Scholar]
  89. MacAlpine HK, Gordan R, Powell SK, Hartemink AJ, MacAlpine DM. 89.  2010. Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading. Genome Res. 20:201–11 [Google Scholar]
  90. MacArthur S, Li XY, Li J, Brown JB, Chu HC. 90.  et al. 2009. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol. 10:R80 [Google Scholar]
  91. Mangone M, Manoharan AP, Thierry-Mieg D, Thierry-Mieg J, Han T. 91.  et al. 2010. The landscape of C. elegans 3′UTRs. Science 329:432–35 [Google Scholar]
  92. McManus CJ, Duff MO, Eipper-Mains J, Graveley BR. 92.  2010. Global analysis of trans-splicing in Drosophila. PNAS 107:12975–79 [Google Scholar]
  93. Mercer TR, Qureshi IA, Gokhan S, Dinger ME, Li G. 93.  et al. 2010. Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. BMC Neurosci. 11:14 [Google Scholar]
  94. Miura P, Shenker S, Andreu-Agullo C, Westholm JO, Lai EC. 94.  2013. Widespread and extensive lengthening of 3′ UTRs in the mammalian brain. Genome Res. 23:812–25 [Google Scholar]
  95. Miura SK, Martins A, Zhang KX, Graveley BR, Zipursky SL. 95.  2013. Probabilistic splicing of Dscam1 establishes identity at the level of single neurons. Cell 155:1166–77 [Google Scholar]
  96. ModENCODE Consort, Roy S, Ernst J, Kharchenko PV, Kheradpour P. 96.  et al. 2010. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330:1787–97 [Google Scholar]
  97. Moorman C, Sun LV, Wang J, de Wit E, Talhout W. 97.  et al. 2006. Hotspots of transcription factor colocalization in the genome of Drosophila melanogaster. PNAS 103:12027–32 [Google Scholar]
  98. Negre N, Brown CD, Ma L, Bristow CA, Miller SW. 98.  et al. 2011. A cis-regulatory map of the Drosophila genome. Nature 471:527–31 [Google Scholar]
  99. Ni X, Zhang YE, Negre N, Chen S, Long M, White KP. 99.  2012. Adaptive evolution and the birth of CTCF binding sites in the Drosophila genome. PLOS Biol. 10:e1001420 [Google Scholar]
  100. Nimura K, Ura K, Shiratori H, Ikawa M, Okabe M. 100.  et al. 2009. A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature 460:287–91 [Google Scholar]
  101. Niu W, Lu ZJ, Zhong M, Sarov M, Murray JI. 101.  et al. 2011. Diverse transcription factor binding features revealed by genome-wide ChIP-seq in C. elegans. Genome Res. 21:245–54 [Google Scholar]
  102. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. 102.  2007. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 130:89–100 [Google Scholar]
  103. Okamura K, Robine N, Liu Y, Liu Q, Lai EC. 103.  2011. R2D2 organizes small regulatory RNA pathways in Drosophila. Mol. Cell. Biol. 31:884–96 [Google Scholar]
  104. 104. Pac. Biosci 2014. Data release: preliminary de novo haploid and diploid assemblies of Drosophila melanogaster. PacBio Blog. Jan. 13. http://blog.pacificbiosciences.com/2014/01/data-release-preliminary-de-novo.html
  105. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. 105.  2008. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40:1413–15 [Google Scholar]
  106. Park D, Lee Y, Bhupindersingh G, Iyer VR. 106.  2013. Widespread misinterpretable ChIP-seq bias in yeast. PLOS ONE 8:e83506 [Google Scholar]
  107. Park PJ. 107.  2009. ChIP-seq: advantages and challenges of a maturing technology. Nat. Rev. Genet. 10:669–80 [Google Scholar]
  108. Paulsen MT, Veloso A, Prasad J, Bedi K, Ljungman EA. 108.  et al. 2013. Use of Bru-Seq and BruChase-Seq for genome-wide assessment of the synthesis and stability of RNA. Methods 67:45–54 [Google Scholar]
  109. Rando OJ. 109.  2012. Combinatorial complexity in chromatin structure and function: revisiting the histone code. Curr. Opin. Genet. Dev. 22:148–55 [Google Scholar]
  110. Rechtsteiner A, Ercan S, Takasaki T, Phippen TM, Egelhofer TA. 110.  et al. 2010. The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny. PLOS Genet. 6:e1001091 [Google Scholar]
  111. Richardson SR, Morell S, Faulkner GJ. 111.  2014. L1 retrotransposons and somatic mosaicism in the brain. Annu. Rev. Genet. 48:1–27 [Google Scholar]
  112. Riddle NC, Jung YL, Gu T, Alekseyenko AA, Asker D. 112.  et al. 2012. Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain. PLOS Genet. 8:e1002954 [Google Scholar]
  113. Riddle NC, Minoda A, Kharchenko PV, Alekseyenko AA, Schwartz YB. 113.  et al. 2011. Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin. Genome Res. 21:147–63 [Google Scholar]
  114. Rinn JL, Chang HY. 114.  2012. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81:145–66 [Google Scholar]
  115. Ruby JG, Jan CH, Bartel DP. 115.  2007. Intronic microRNA precursors that bypass Drosha processing. Nature 448:83–86 [Google Scholar]
  116. Ruby JG, Jan CH, Player C, Axtell MJ, Lee W. 116.  et al. 2006. Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127:1193–207 [Google Scholar]
  117. Saito K, Inagaki S, Mituyama T, Kawamura Y, Ono Y. 117.  et al. 2009. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature 461:1296–99 [Google Scholar]
  118. Saloura V, Cho H-S, Kyiotani K, Alachkar H, Zuo Z. 118.  et al. 2015. WHSC1 promotes oncogenesis through regulation of NIMA-related kinase-7 in squamous cell carcinoma of the head and neck. Mol. Cancer Res. 13:293–304 [Google Scholar]
  119. Schwartz YB, Linder-Basso D, Kharchenko PV, Tolstorukov MY, Kim M. 119.  et al. 2012. Nature and function of insulator protein binding sites in the Drosophila genome. Genome Res. 22:2188–98 [Google Scholar]
  120. Shindo Y, Nozaki T, Saito R, Tomita M. 120.  2013. Computational analysis of associations between alternative splicing and histone modifications. FEBS Lett. 587:516–21 [Google Scholar]
  121. Smibert P, Miura P, Westholm JO, Shenker S, May G. 121.  et al. 2012. Global patterns of tissue-specific alternative polyadenylation in Drosophila. Cell Rep. 1:277–89 [Google Scholar]
  122. Stoeckius M, Maaskola J, Colombo T, Rahn HP, Friedlander MR. 122.  et al. 2009. Large-scale sorting of C. elegans embryos reveals the dynamics of small RNA expression. Nat. Methods 6:745–51 [Google Scholar]
  123. Sturgill D, Malone JH, Sun X, Smith HE, Rabinow L. 123.  et al. 2013. Design of RNA splicing analysis null models for post hoc filtering of Drosophila head RNA-Seq data with the splicing analysis kit (Spanki). BMC Bioinform. 14:320 [Google Scholar]
  124. Tagu D, Colbourne JK, Negre N. 124.  2014. Genomic data integration for ecological and evolutionary traits in non-model organisms. BMC Genomics 15:490 [Google Scholar]
  125. Teytelman L, Thurtle DM, Rine J, van Oudenaarden A. 125.  2013. Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins. PNAS 110:18602–7 [Google Scholar]
  126. Tome JM, Ozer A, Pagano JM, Gheba D, Schroth GP, Lis JT. 126.  2014. Comprehensive analysis of RNA-protein interactions by high-throughput sequencing-RNA affinity profiling. Nat. Methods 11:683–88 [Google Scholar]
  127. Trapnell C, Roberts A, Goff L, Pertea G, Kim D. 127.  et al. 2012. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7:562–78 [Google Scholar]
  128. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G. 128.  et al. 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28:511–15 [Google Scholar]
  129. Van Nostrand EL, Kim SK. 129.  2013. Integrative analysis of C. elegans modENCODE ChIP-seq data sets to infer gene regulatory interactions. Genome Res. 23:941–53 [Google Scholar]
  130. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L. 130.  et al. 2008. Alternative isoform regulation in human tissue transcriptomes. Nature 456:470–76 [Google Scholar]
  131. Ward LD, Kellis M. 131.  2012. Interpreting noncoding genetic variation in complex traits and human disease. Nat. Biotechnol. 30:1095–106 [Google Scholar]
  132. Wen J, Mohammed J, Bortolamiol-Becet D, Tsai H, Robine N. 132.  et al. 2014. Diversity of miRNAs, siRNAs, and piRNAs across 25 Drosophila cell lines. Genome Res. 24:1236–50 [Google Scholar]
  133. Westholm JO, Ladewig E, Okamura K, Robine N, Lai EC. 133.  2012. Common and distinct patterns of terminal modifications to mirtrons and canonical microRNAs. RNA 18:177–92 [Google Scholar]
  134. Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E. 134.  et al. 2014. A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell 159:200–14 [Google Scholar]
  135. Yang Q, Hua J, Wang L, Xu B, Zhang H. 135.  et al. 2013. MicroRNA and piRNA profiles in normal human testis detected by next generation sequencing. PLOS ONE 8:e66809 [Google Scholar]
  136. Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL. 136.  et al. 2012. LincRNA-p21 suppresses target mRNA translation. Mol. Cell 47:648–55 [Google Scholar]
  137. Young RS, Marques AC, Tibbit C, Haerty W, Bassett AR. 137.  et al. 2012. Identification and properties of 1,119 candidate lincRNA loci in the Drosophila melanogaster genome. Genome Biol. Evol. 4:427–42 [Google Scholar]
  138. Zentner GE, Henikoff S. 138.  2014. High-resolution digital profiling of the epigenome. Nat. Rev. Genet. 15:814–27 [Google Scholar]
  139. Zhao Q, Rank G, Tan YT, Li H, Moritz RL. 139.  et al. 2009. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat. Struct. Mol. Biol. 16:304–11 [Google Scholar]
  140. Zhong M, Niu W, Lu ZJ, Sarov M, Murray JI. 140.  et al. 2010. Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response. PLOS Genet. 6:e1000848 [Google Scholar]
  141. Zhu S, Wang G, Liu B, Wang Y. 141.  2013. Modeling exon expression using histone modifications. PLOS ONE 8:e67448 [Google Scholar]
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