Skip to main content

Molecular Biology Basics in the “Omics” Era: Genes to Proteins

  • Chapter
Molecular Oncology Testing for Solid Tumors

Abstract

This chapter attempts to summarize what is known regarding the organization and functional role of DNA and RNA in normal cell growth and differentiation that may be relevant to cancer cells. Information accruing over the last 15 years and particularly the last 5–10 years is emphasized but early discoveries important to the development of our current understanding are referenced. New technologies such as next generation DNA sequencing and its derivatives including ChIP-seq, RNA-seq, and chromosome conformation capture techniques along with huge collaborative projects including sequencing of the human genome, ENCODE, the Roadmap Epigenomics Program, and most recently the 4D Nucleome project are extending the ability of medical scientists to probe the organization of chromatin and through this determine the regulatory networks of specific cell types. While this chapter can only touch briefly on this broad range of topics it is hoped that it can provide a starting point for expanding understanding of the many opportunities as well as some of the potential pitfalls that are certain to arise in the growing field of cancer molecular testing.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. 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(6822):860–921. PM:11237011, http://dx.doi.org/10.1038/35057062.

    CAS  PubMed  Google Scholar 

  2. Elnitski L. Regulatory and epigenetic landscapes of mammalian genomes: YouTube. National Institutes of Health National Human Genome Research Institute. 2014. Curr Topic Genome Anal. 2014. https://www.youtube.com/watch?v = C2VG_71XhH4.

  3. Elnitski L. Regulatory and epigenetic landscapes of mammalian genomes: Lec05.pdf. National Institutes of Health National Human Genome Research Institute. 2014. Curr Topic Genome Anal. 2014. http://www.genome.gov/Pages/Research/IntramuralResearch/DIRCalendar/CTGA2014/CTGA2014_Lec05_color.pdf.

  4. Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, et al. Defining functional DNA elements in the human genome. Proc Natl Acad Sci U S A. 2014;111(17):6131–8. PM:24753594.

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Boyd C, Boyle DP. Molecular diagnosis on tissues and cells: how it affects training and will affect practice in the future. Cytopathology. 2012;23(5):286–94. PM:22846108.

    CAS  PubMed  Google Scholar 

  6. Pant S, Weiner R, Marton MJ. Navigating the rapids: the development of regulated next-generation sequencing-based clinical trial assays and companion diagnostics. Front Oncol. 2014;4:78. PM:24860780.

    PubMed Central  PubMed  Google Scholar 

  7. Reid JB, Ross JJ. Mendel’s genes: toward a full molecular characterization. Genetics. 2011;189(1):3–10. PM:21908742; http://www.genetics.org/content/189/1/3.full.pdf + html.

  8. Garrod AE. The incidence of alkaptonuria: a study in chemical individuality. 1902. Mol Med. 1996;2(3):274–82. PM:8784780.

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Beadle GW, Tatum EL. Genetic control of biochemical reactions in Neurospora. Proc Natl Acad Sci U S A. 1941;27(11):499–506. PM:16588492.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Avery OT, Macleod CM, McCarty M. Studies on the chemical nature of the substance inducing transformation of Pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III. J Exp Med. 1944;79(2):137–58. PM:19871359.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Watson JD, Crick FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;171(4356):737–8. PM:13054692.

    CAS  PubMed  Google Scholar 

  12. Crick FH. On protein synthesis. Symp Soc Exp Biol. 1958;12:138–63. PM:13580867.

    CAS  PubMed  Google Scholar 

  13. Crick F. Central dogma of molecular biology. Nature. 1970;227(5258):561–3. PM:4913914.

    CAS  PubMed  Google Scholar 

  14. Hoagland MB, Zamecnik PC, Stephenson ML. Intermediate reactions in protein biosynthesis. Biochim Biophys Acta. 1957;24(1):215–6. PM:13426231.

    CAS  PubMed  Google Scholar 

  15. Hoagland MB. Commentary on ‘Intermediate Reactions in Protein Biosynthesis’. Biochim Biophys Acta. 1989;1000:103–5. PM:2673354.

    CAS  PubMed  Google Scholar 

  16. Littauer UZ, Inouye H. Regulation of tRNA. Annu Rev Biochem. 1973;42:439–70. PM:4199854.

    CAS  PubMed  Google Scholar 

  17. Attardi G, Amaldi F. Structure and synthesis of ribosomal RNA. Annu Rev Biochem. 1970;39:183–226. PM:4920820.

    CAS  PubMed  Google Scholar 

  18. Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961;3:318–56. PM:13718526.

    CAS  PubMed  Google Scholar 

  19. Gros F, Hiatt H, Gilbert W, Kurland CG, Risebrough RW, Watson JD. Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli. Nature. 1961;190:581–5. PM:13708983.

    CAS  PubMed  Google Scholar 

  20. Brenner S, Jacob F, Meselson M. An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature. 1961;190:576–81. PM:20446365.

    CAS  PubMed  Google Scholar 

  21. Speyer JF, Lengyel P, Basilio C, Ochoa S. Synthetic polynucleotides and the amino acid code. II. Proc Natl Acad Sci U S A. 1962;48:63–8. PM:13915740.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Martin RG, Matthaei JH, Jones OW, Nirenberg MW. Ribonucleotide composition of the genetic code. Biochem Biophys Res Commun. 1962;6:410–4. PM:14470439.

    CAS  PubMed  Google Scholar 

  23. Nirenberg MW, Matthaei JH, Jones OW, Martin RG, Barondes SH. Approximation of genetic code via cell-free protein synthesis directed by template RNA. Fed Proc. 1963;22:55–61. PM:13938750.

    CAS  PubMed  Google Scholar 

  24. Leder P, Nirenberg MW. RNA Codewords and protein synthesis, 3. On the nucleotide sequence of a cysteine and a leucine RNA codeword. Proc Natl Acad Sci U S A. 1964;52:1521–9. PM:14243527.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Sanger F, Donelson JE, Coulson AR, Kossel H, Fischer D. Use of DNA polymerase I primed by a synthetic oligonucleotide to determine a nucleotide sequence in phage fl DNA. Proc Natl Acad Sci U S A. 1973;70(4):1209–13. PM:4577794.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Jackson DA, Symons RH, Berg P. Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc Natl Acad Sci U S A. 1972;69(10):2904–9. PM:4342968.

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985;230(4732):1350–4. PM:2999980.

    CAS  PubMed  Google Scholar 

  28. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63. PM:19015660.

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Metzker ML. Sequencing technologies: the next generation. Nat Rev Genet. 2010;11(1):31–46. PM:19997069.

    CAS  PubMed  Google Scholar 

  30. Stamatoyannopoulos JA. What does our genome encode? Genome Res. 2012;22(9):1602–11. PM:22955972.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Gerstein MB, Bruce C, Rozowsky JS, Zheng D, Du J, Korbel JO, et al. What is a gene, post-ENCODE? History and updated definition. Genome Res. 2007;17(6):669–81. PM:17567988.

    CAS  PubMed  Google Scholar 

  32. Dieci G, Fiorino G, Castelnuovo M, Teichmann M, Pagano A. The expanding RNA polymerase III transcriptome. Trends Genet. 2007;23(12):614–22. PM:17977614.

    CAS  PubMed  Google Scholar 

  33. Hopper AK, Pai DA, Engelke DR. Cellular dynamics of tRNAs and their genes. FEBS Lett. 2010;584(2):310–7. PM:19931532.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Orioli A, Pascali C, Pagano A, Teichmann M, Dieci G. RNA polymerase III transcription control elements: themes and variations. Gene. 2012;493(2):185–94. PM:21712079.

    CAS  PubMed  Google Scholar 

  35. Dieci G, Conti A, Pagano A, Carnevali D. Identification of RNA polymerase III-transcribed genes in eukaryotic genomes. Biochim Biophys Acta. 2013;1829(3–4):296–305. PM:23041497.

    CAS  PubMed  Google Scholar 

  36. Berg JM, Tymoczko JL, Stryer L. Eukaryotic transcription and translation are separated in space and time. In: Berg JM, Tymoczko JL, Stryer L, editors. Biochemistry. 5th ed. New York, NY: W H Freeman; 2002. http://www.ncbi.nlm.nih.gov/books/NBK22433/.

    Google Scholar 

  37. Fuda NJ, Ardehali MB, Lis JT. Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature. 2009;461(7261):186–92. PM:19741698.

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Berg JM, Tymoczko JL, Stryer L. The transcription products of all three eukaryotic polymerases are processed. In: Berg JM, Tymoczko JL, Stryer L, editors. Biochemistry. 5th ed. New York, NY: W H Freeman; 2002. http://www.ncbi.nlm.nih.gov/books/NBK22563/.

    Google Scholar 

  39. Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet. 2006;7:29–59. PM:16719718.

    CAS  PubMed  Google Scholar 

  40. Subramanian D. Computational genefinding. OpenStax CNX. 2007. http://cnx.org/contents/9b99e2ed-9865-46dd-92a8-39ad69766bd5@1@1.

  41. Clancy S. DNA transcription. Nat Edu. 2008;1:41. http://www.nature.com/scitable/topicpage/dna-transcription-426.

    Google Scholar 

  42. Smallwood A, Ren B. Genome organization and long-range regulation of gene expression by enhancers. Curr Opin Cell Biol. 2013;25(3):387–94. PM:23465541.

    PubMed Central  CAS  PubMed  Google Scholar 

  43. Rubinstein M, de Souza FS. Evolution of transcriptional enhancers and animal diversity. Philos Trans R Soc Lond B Biol Sci. 2013;368(1632):20130017. PM:24218630.

    PubMed Central  PubMed  Google Scholar 

  44. Jin F, Li Y, Dixon JR, Selvaraj S, Ye Z, Lee AY, et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature. 2013;503(7475):290–4. PM:24141950.

    CAS  PubMed  Google Scholar 

  45. Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature. 2012;489(7414):109–13. PM:22955621.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Hubner MR, Eckersley-Maslin MA, Spector DL. Chromatin organization and transcriptional regulation. Curr Opin Genet Dev. 2013;23(2):89–95. PM:23270812.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Krivega I, Dean A. Enhancer and promoter interactions-long distance calls. Curr Opin Genet Dev. 2012;22(2):79–85. PM:22169023.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010;467(7314):430–5. PM:20720539.

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Phillips-Cremins JE, Sauria ME, Sanyal A, Gerasimova TI, Lajoie BR, Bell JS, et al. Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell. 2013;153(6):1281–95. PM:23706625.

    PubMed Central  CAS  PubMed  Google Scholar 

  50. Kind J, van Steensel B. Genome-nuclear lamina interactions and gene regulation. Curr Opin Cell Biol. 2010;22(3):320–5. PM:20444586.

    CAS  PubMed  Google Scholar 

  51. ENCODE Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74. PM:22955616.

    Google Scholar 

  52. Neph S, Vierstra J, Stergachis AB, Reynolds AP, Haugen E, Vernot B, et al. An expansive human regulatory lexicon encoded in transcription factor footprints. Nature. 2012;489(7414):83–90. PM:22955618.

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Kieffer-Kwon KR, Tang Z, Mathe E, Qian J, Sung MH, Li G, et al. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell. 2013;155(7):1507–20. PM:24360274.

    CAS  PubMed  Google Scholar 

  54. Nord AS, Blow MJ, Attanasio C, Akiyama JA, Holt A, Hosseini R, et al. Rapid and pervasive changes in genome-wide enhancer usage during mammalian development. Cell. 2013;155(7):1521–31. PM:24360275.

    PubMed Central  CAS  PubMed  Google Scholar 

  55. Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM. A census of human transcription factors: function, expression and evolution. Nat Rev Genet. 2009;10(4):252–63. PM:19274049.

    CAS  PubMed  Google Scholar 

  56. Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, et al. The accessible chromatin landscape of the human genome. Nature. 2012;489(7414):75–82. PM:22955617.

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Neph S, Stergachis AB, Reynolds A, Sandstrom R, Borenstein E, Stamatoyannopoulos JA. Circuitry and dynamics of human transcription factor regulatory networks. Cell. 2012;150(6):1274–86. PM:22959076.

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Frankel N. Multiple layers of complexity in cis-regulatory regions of developmental genes. Dev Dyn. 2012;241(12):1857–66. PM:22972751.

    CAS  PubMed  Google Scholar 

  59. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Processing of Eukaryotic mRNA. In: Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J, editors. Molecular Cell Biology. 4th ed. New York, NY: W H Freeman; 2000. http://www.ncbi.nlm.nih.gov/books/NBK21563/.

    Google Scholar 

  60. Clancy S. RNA splicing: introns, exons and spliceosome. Nature Education. 2008. 1:31. http://www.nature.com/scitable/topicpage/rna-splicing-introns-exons-and-spliceosome-12375#.

  61. Roca X, Krainer AR, Eperon IC. Pick one, but be quick: 5′ splice sites and the problems of too many choices. Genes Dev. 2013;27(2):129–44. PM:23348838.

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Kiss T. Biogenesis of small nuclear RNPs. J Cell Sci. 2004;117(Pt 25):5949–51. PM:15564372.

    CAS  PubMed  Google Scholar 

  63. Paule MR, White RJ. Survey and summary: transcription by RNA polymerases I and III. Nucleic Acids Res. 2000;28(6):1283–98. PM:10684922.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, et al. Alternative isoform regulation in human tissue transcriptomes. Nature. 2008;456(7221):470–6. PM:18978772.

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008;40(12):1413–5. PM:18978789.

    CAS  PubMed  Google Scholar 

  66. Hallegger M, Llorian M, Smith CW. Alternative splicing: global insights. FEBS J. 2010;277(4):856–66. PM:20082635.

    CAS  PubMed  Google Scholar 

  67. Matlin AJ, Clark F, Smith CW. Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol. 2005;6(5):386–98. PM:15956978.

    CAS  PubMed  Google Scholar 

  68. Goodfellow SJ, Zomerdijk JC. Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes. Subcell Biochem. 2013;61:211–36. PM:23150253.

    CAS  PubMed  Google Scholar 

  69. Stults DM, Killen MW, Pierce HH, Pierce AJ. Genomic architecture and inheritance of human ribosomal RNA gene clusters. Genome Res. 2008;18(1):13–8. PM:18025267.

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Henderson AS, Warburton D, Atwood KC. Location of ribosomal DNA in the human chromosome complement. Proc Natl Acad Sci U S A. 1972;69(11):3394–8. PM:4508329.

    PubMed Central  CAS  PubMed  Google Scholar 

  71. Nemeth A, Langst G. Genome organization in and around the nucleolus. Trends Genet. 2011;27(4):149–56. PM:21295884.

    CAS  PubMed  Google Scholar 

  72. Floutsakou I, Agrawal S, Nguyen TT, Seoighe C, Ganley AR, McStay B. The shared genomic architecture of human nucleolar organizer regions. Genome Res. 2013;23(12):2003–12. PM:23990606.

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Grob A, Colleran C, McStay B. Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division. Genes Dev. 2014;28(3):220–30. PM:24449107.

    PubMed Central  CAS  PubMed  Google Scholar 

  74. Prieto JL, McStay B. Nucleolar biogenesis: the first small steps. Biochem Soc Trans. 2005;33(Pt 6):1441–3. PM:16246141.

    CAS  PubMed  Google Scholar 

  75. Sorensen PD, Frederiksen S. Characterization of human 5S rRNA genes. Nucleic Acids Res. 1991;19(15):4147–51. PM:1870970.

    PubMed Central  CAS  PubMed  Google Scholar 

  76. Sorensen PD, Lomholt B, Frederiksen S, Tommerup N. Fine mapping of human 5S rRNA genes to chromosome 1q42.11–q42.13. Cytogenet Cell Genet. 1991;57(1):26–9. PM:1855389.

    CAS  PubMed  Google Scholar 

  77. Ciganda M, Williams N. Eukaryotic 5S rRNA biogenesis. Wiley Interdiscip Rev RNA. 2011;2(4):523–33. PM:21957041.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Reichow SL, Hamma T, Ferre-D’Amare AR, Varani G. The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res. 2007;35(5):1452–64. PM:17284456.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Dieci G, Preti M, Montanini B. Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics. 2009;94(2):83–8. PM:19446021.

    CAS  PubMed  Google Scholar 

  80. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Processing of rRNA and tRNA. In: Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J, editors. Molecular cell biology. 4th ed. New York, NY: W H Freeman; 2000. http://www.ncbi.nlm.nih.gov/books/NBK21729/.

    Google Scholar 

  81. Bai B, Yegnasubramanian S, Wheelan SJ, Laiho M. RNA-Seq of the nucleolus reveals abundant SNORD44-derived small RNAs. PLoS One. 2014;9(9), e107519. PM:25203660.

    PubMed Central  PubMed  Google Scholar 

  82. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. The three roles of RNA in protein synthesis. In: Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J, editors. Molecular cell biology. 4th ed. New York, NY: W H Freeman; 2000. http://www.ncbi.nlm.nih.gov/books/NBK21603/.

    Google Scholar 

  83. Tocchini-Valentini GD, Fruscoloni P, Tocchini-Valentini GP. Processing of multiple-intron-containing pretRNA. Proc Natl Acad Sci U S A. 2009;106(48):20246–51. PM:19910528; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787110.

    PubMed Central  CAS  PubMed  Google Scholar 

  84. Deutscher MP. 7 tRNA nucleotidyltransferase. In: Boyle DP, editor. The enzymes. Amsterdam: Elsevier; 1982. p. 183–215.

    Google Scholar 

  85. Xiong Y, Steitz TA. A story with a good ending: tRNA 3′-end maturation by CCA-adding enzymes. Curr Opin Struct Biol. 2006;16(1):12–7. PM:16364630.

    CAS  PubMed  Google Scholar 

  86. Berg JM, Tymoczko JL, Stryer L. Protein synthesis requires the translation of nucleotide sequences into amino acid. In: Berg JM, Tymoczko JL, Stryer L, editors. Biochemistry. 5th ed. New York, NY: W H Freeman; 2002. http://www.ncbi.nlm.nih.gov/books/NBK22421/.

    Google Scholar 

  87. Anderson P, Ivanov P. TRNA fragments in human health and disease. FEBS Lett. 2014;588:4297–304. PM:25220675.

    PubMed Central  CAS  PubMed  Google Scholar 

  88. Pavon-Eternod M, Gomes S, Rosner MR, Pan T. Overexpression of initiator methionine tRNA leads to global reprogramming of tRNA expression and increased proliferation in human epithelial cells. RNA. 2013;19(4):461–6. PM:23431330.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Hernandez-Verdun D, Roussel P, Thiry M, Sirri V, Lafontaine DL. The nucleolus: structure/function relationship in RNA metabolism. Wiley Interdiscip Rev RNA. 2010;1(3):415–31. PM:21956940.

    CAS  PubMed  Google Scholar 

  90. Heliot L, Kaplan H, Lucas L, Klein C, Beorchia A, Doco-Fenzy M, et al. Electron tomography of metaphase nucleolar organizer regions: evidence for a twisted-loop organization. Mol Biol Cell. 1997;8(11):2199–216. PM:9362063.

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Ferguson-Smith MA, Handmaker SD. Observations on the satellited human chromosomes. Lancet. 1961;1(7178):638–40. PM:13698902.

    CAS  PubMed  Google Scholar 

  92. Miller DA, Dev VG, Tantravahi R, Miller OJ. Suppression of human nucleolus organizer activity in mouse-human somatic hybrid cells. Exp Cell Res. 1976;101(2):235–43. PM:61125.

    CAS  PubMed  Google Scholar 

  93. Roussel P, Andre C, Comai L, Hernandez-Verdun D. The rDNA transcription machinery is assembled during mitosis in active NORs and absent in inactive NORs. J Cell Biol. 1996;133(2):235–46. PM:8609158.

    CAS  PubMed  Google Scholar 

  94. Sirri V, Hernandez-Verdun D, Roussel P. Cyclin-dependent kinases govern formation and maintenance of the nucleolus. J Cell Biol. 2002;156(6):969–81. PM:11901165.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Miller OJ, Miller DA, Dev VG, Tantravahi R, Croce CM. Expression of human and suppression of mouse nucleolus organizer activity in mouse-human somatic cell hybrids. Proc Natl Acad Sci U S A. 1976;73(12):4531–5. PM:1070003.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Mais C, Wright JE, Prieto JL, Raggett SL, McStay B. UBF-binding site arrays form pseudo-NORs and sequester the RNA polymerase I transcription machinery. Genes Dev. 2005;19(1):50–64. PM:15598984.

    PubMed Central  CAS  PubMed  Google Scholar 

  97. Kozak M. Initiation of translation in prokaryotes and eukaryotes. Gene. 1999;234(2):187–208. PM:10395892.

    CAS  PubMed  Google Scholar 

  98. Berg JM, Tymoczko JL, Stryer L. Eukaryotic protein synthesis differs from prokaryotic protein synthesis primarily in translation initiation. In: Berg JM, Tymoczko JL, Stryer L, editors. Biochemistry. 5th ed. New York, NY: W H Freeman; 2002. http://www.ncbi.nlm.nih.gov/books/NBK22531/.

    Google Scholar 

  99. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Stepwise formation of proteins on ribosomes. In: Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J, editors. Molecular cell biology. 4th ed. New York, NY: W H Freeman; 2000. http://www.ncbi.nlm.nih.gov/books/NBK21653/.

    Google Scholar 

  100. Berg JM, Tymoczko JL. A Ribosome is a ribonucleoprotein particle (70S) made of a small (30S) and a large (50S) subunit. In: Berg JM, Tymoczko JL, Stryer L, editors. Biochemistry. 5th ed. New York, NY: W H Freeman; 2002. http://www.ncbi.nlm.nih.gov/books/NBK22335/.

    Google Scholar 

  101. Clancy S, Brown W. Translation: DNA to mRNA to protein. Nat Edu. 2008;1:101. http://www.nature.com/scitable/topicpage/translation-dna-to-mrna-to-protein-393.

    Google Scholar 

  102. Jackson RJ, Standart N. How do microRNAs regulate gene expression? Sci STKE. 2007;2007(367):re1. PM:17200520.

    PubMed  Google Scholar 

  103. Clancy S. RNA functions. Nat Edu. 2008;1:102. http://www.nature.com/scitable/topicpage/rna-functions-352#.

  104. Valinezhad OA, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genomics. 2014;2014:970607. PM:25180174.

    Google Scholar 

  105. Griffiths-Jones S. miRBase 21 finally arrives. miRBase, University of Manchester. 2014. http://www.mirbase.org/blog/2014/06/mirbase-21-finally-arrives/.

  106. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92–105. PM:18955434.

    PubMed Central  CAS  PubMed  Google Scholar 

  107. Farazi TA, Juranek SA, Tuschl T. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development. 2008;135(7):1201–14. PM:18287206.

    CAS  PubMed  Google Scholar 

  108. Watanabe T, Takeda A, Tsukiyama T, Mise K, Okuno T, Sasaki H, et al. Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev. 2006;20(13):1732–43. PM:16766679.

    PubMed Central  CAS  PubMed  Google Scholar 

  109. Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, et al. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature. 2008;453(7194):534–8. PM:18404147.

    PubMed Central  CAS  PubMed  Google Scholar 

  110. Babiarz JE, Ruby JG, Wang Y, Bartel DP, Blelloch R. Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev. 2008;22(20):2773–85. PM:18923076.

    PubMed Central  CAS  PubMed  Google Scholar 

  111. Claycomb JM. Ancient endo-siRNA pathways reveal new tricks. Curr Biol. 2014;24(15):R703–15. PM:25093565.

    CAS  PubMed  Google Scholar 

  112. Ghorai A, Ghosh U. miRNA gene counts in chromosomes vary widely in a species and biogenesis of miRNA largely depends on transcription or post-transcriptional processing of coding genes. Front Genet. 2014;5:100. PM:24808907.

    PubMed Central  PubMed  Google Scholar 

  113. Marco A, Ninova M, Ronshaugen M, Griffiths-Jones S. Clusters of microRNAs emerge by new hairpins in existing transcripts. Nucleic Acids Res. 2013;41(16):7745–52. PM:23775791.

    PubMed Central  CAS  PubMed  Google Scholar 

  114. Godnic I, Zorc M, Jevsinek SD, Calin GA, Horvat S, Dovc P, et al. Genome-wide and species-wide in silico screening for intragenic MicroRNAs in human, mouse and chicken. PLoS One. 2013;8(6), e65165. PM:23762306.

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60. PM:15372072.

    PubMed Central  CAS  PubMed  Google Scholar 

  116. Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol. 2006;13(12):1097–101. PM:17099701.

    CAS  PubMed  Google Scholar 

  117. Schanen BC, Li X. Transcriptional regulation of mammalian miRNA genes. Genomics. 2011;97(1):1–6. PM:20977933.

    PubMed Central  CAS  PubMed  Google Scholar 

  118. Kunej T, Godnic I, Horvat S, Zorc M, Calin GA. Cross talk between microRNA and coding cancer genes. Cancer J. 2012;18(3):223–31. PM:22647358.

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Chowdhury D, Choi YE, Brault ME. Charity begins at home: non-coding RNA functions in DNA repair. Nat Rev Mol Cell Biol. 2013;14(3):181–9. PM:23385724.

    PubMed Central  CAS  PubMed  Google Scholar 

  120. Ge XQ, Lin H. Noncoding RNAs in the regulation of DNA replication. Trends Biochem Sci. 2014;39(8):341–3. PM:25027733.

    PubMed Central  CAS  PubMed  Google Scholar 

  121. Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, et al. Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A. 2006;103(46):17337–42. PM:17085592.

    PubMed Central  CAS  PubMed  Google Scholar 

  122. Suzuki K, Kelleher AD. Transcriptional regulation by promoter targeted RNAs. Curr Top Med Chem. 2009;9(12):1079–87. PM:19860708.

    CAS  PubMed  Google Scholar 

  123. Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy. Adv Drug Deliv Rev. 2014;81:75–93. PM:25220354.

    PubMed  Google Scholar 

  124. The ENCODE Project Consortium. A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 2011;9(4), e1001046. PM:21526222.

    PubMed Central  Google Scholar 

  125. Siggens L, Ekwall K. Epigenetics, chromatin and genome organization: recent advances from the ENCODE project. J Intern Med. 2014;276(3):201–14. PM:24605849.

    CAS  PubMed  Google Scholar 

  126. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. Landscape of transcription in human cells. Nature. 2012;489(7414):101–8. PM:22955620.

    PubMed Central  CAS  PubMed  Google Scholar 

  127. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012;22(9):1760–74. PM:22955987.

    PubMed Central  CAS  PubMed  Google Scholar 

  128. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89. PM:22955988, http://genome.cshlp.org/content/22/9/1775.full.pdf+html.

    PubMed Central  CAS  PubMed  Google Scholar 

  129. de Koning AP, Gu W, Castoe TA, Batzer MA, Pollock DD. Repetitive elements may comprise over two-thirds of the human genome. PLoS Genet. 2011;7(12), e1002384. PM:22144907.

    PubMed Central  PubMed  Google Scholar 

  130. Richard GF, Kerrest A, Dujon B. Comparative genomics and molecular dynamics of DNA repeats in eukaryotes. Microbiol Mol Biol Rev. 2008;72(4):686–727. PM:19052325.

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Levin HL, Moran JV. Dynamic interactions between transposable elements and their hosts. Nat Rev Genet. 2011;12(9):615–27. PM:21850042.

    PubMed Central  CAS  PubMed  Google Scholar 

  132. Burns KH, Boeke JD. Human transposon tectonics. Cell. 2012;149(4):740–52. PM:22579280.

    PubMed Central  CAS  PubMed  Google Scholar 

  133. Cordaux R, Batzer MA. The impact of retrotransposons on human genome evolution. Nat Rev Genet. 2009;10(10):691–703. PM:19763152.

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Ishizu H, Siomi H, Siomi MC. Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines. Genes Dev. 2012;26(21):2361–73. PM:23124062.

    PubMed Central  CAS  PubMed  Google Scholar 

  135. Ha H, Song J, Wang S, Kapusta A, Feschotte C, Chen KC, et al. A comprehensive analysis of piRNAs from adult human testis and their relationship with genes and mobile elements. BMC Genomics. 2014;15:545. PM:24981367.

    PubMed Central  PubMed  Google Scholar 

  136. Georgiou I, Noutsopoulos D, Dimitriadou E, Markopoulos G, Apergi A, Lazaros L, et al. Retrotransposon RNA expression and evidence for retrotransposition events in human oocytes. Hum Mol Genet. 2009;18(7):1221–8. PM:19147684.

    CAS  PubMed  Google Scholar 

  137. Macia A, Munoz-Lopez M, Cortes JL, Hastings RK, Morell S, Lucena-Aguilar G, et al. Epigenetic control of retrotransposon expression in human embryonic stem cells. Mol Cell Biol. 2011;31(2):300–16. PM:21041477.

    PubMed Central  CAS  PubMed  Google Scholar 

  138. Belancio VP, Roy-Engel AM, Pochampally RR, Deininger P. Somatic expression of LINE-1 elements in human tissues. Nucleic Acids Res. 2010;38(12):3909–22. PM:20215437.

    PubMed Central  CAS  PubMed  Google Scholar 

  139. Belancio VP, Roy-Engel AM, Deininger PL. All y’all need to know ’bout retroelements in cancer. Semin Cancer Biol. 2010;20(4):200–10. PM:20600922.

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Beck CR, Collier P, Macfarlane C, Malig M, Kidd JM, Eichler EE, et al. LINE-1 retrotransposition activity in human genomes. Cell. 2010;141(7):1159–70. PM:20602998.

    PubMed Central  CAS  PubMed  Google Scholar 

  141. Terasaki N, Goodier JL, Cheung LE, Wang YJ, Kajikawa M, Kazazian Jr HH, et al. In vitro screening for compounds that enhance human L1 mobilization. PLoS One. 2013;8(9), e74629. PM:24040300.

    PubMed Central  CAS  PubMed  Google Scholar 

  142. Muotri AR, Zhao C, Marchetto MC, Gage FH. Environmental influence on L1 retrotransposons in the adult hippocampus. Hippocampus. 2009;19(10):1002–7. PM:19771587.

    PubMed Central  CAS  PubMed  Google Scholar 

  143. Gorbunova V, Boeke JD, Helfand SL, Sedivy JM. Human genomics. Sleeping dogs of the genome. Science. 2014;346(6214):1187–8. PM:25477445.

    CAS  PubMed  Google Scholar 

  144. De CM, Criscione SW, Peckham EJ, Hillenmeyer S, Hamm EA, Manivannan J, et al. Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell. 2013;12(2):247–56. PM:23360310.

    Google Scholar 

  145. De CM, Criscione SW, Peterson AL, Neretti N, Sedivy JM, Kreiling JA. Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues. Aging (Albany NY). 2013;5(12):867–83. PM:24323947.

    Google Scholar 

  146. Kugel S, Mostoslavsky R. Chromatin and beyond: the multitasking roles for SIRT6. Trends Biochem Sci. 2014;39(2):72–81. PM:24438746.

    PubMed Central  CAS  PubMed  Google Scholar 

  147. Criscione SW, Zhang Y, Thompson W, Sedivy JM, Neretti N. Transcriptional landscape of repetitive elements in normal and cancer human cells. BMC Genomics. 2014;15:583. PM:25012247.

    PubMed Central  PubMed  Google Scholar 

  148. Solyom S, Kazazian Jr HH. Mobile elements in the human genome: implications for disease. Genome Med. 2012;4(2):12. PM:22364178.

    PubMed Central  CAS  PubMed  Google Scholar 

  149. Hancks DC, Kazazian Jr HH. Active human retrotransposons: variation and disease. Curr Opin Genet Dev. 2012;22(3):191–203. PM:22406018.

    PubMed Central  CAS  PubMed  Google Scholar 

  150. Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, et al. Identification and analysis of functional elements in 1 % of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816. PM:17571346.

    CAS  PubMed  Google Scholar 

  151. Affymetrix. GeneChip Human Tiling Arrays. Affymetrix. 2014. http://media.affymetrix.com/support/technical/datasheets/human_tiling_datasheet.pdf.

  152. Emanuelsson O, Nagalakshmi U, Zheng D, Rozowsky JS, Urban AE, Du J, et al. Assessing the performance of different high-density tiling microarray strategies for mapping transcribed regions of the human genome. Genome Res. 2007;17(6):886–97. PM:17119069.

    PubMed Central  CAS  PubMed  Google Scholar 

  153. Institute for Systems Biology. RepeatMasker. Institute for Systems Biology. 2014. http://repeatmasker.org/.

  154. Song L, Zhang Z, Grasfeder LL, Boyle AP, Giresi PG, Lee BK, et al. Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity. Genome Res. 2011;21(10):1757–67. PM:21750106.

    PubMed Central  CAS  PubMed  Google Scholar 

  155. Fullwood MJ, Wei CL, Liu ET, Ruan Y. Next-generation DNA sequencing of paired-end tags (PET) for transcriptome and genome analyses. Genome Res. 2009;19(4):521–32. PM:19339662.

    PubMed Central  CAS  PubMed  Google Scholar 

  156. HGNC. HOXD@ homeobox D cluster [Homo sapiens (human)]. HUGO Gene Nomenclature Committee (HGNC). 2014. http://www.ncbi.nlm.nih.gov/gene/3230/.

  157. Harrow J, Denoeud F, Frankish A, Reymond A, Chen CK, Chrast J, et al. GENCODE: producing a reference annotation for ENCODE. Genome Biol. 2006;7 Suppl 1:S4–9. PM:16925838.

    PubMed Central  PubMed  Google Scholar 

  158. Denoeud F, Kapranov P, Ucla C, Frankish A, Castelo R, Drenkow J, et al. Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Res. 2007;17(6):746–59. PM:17567994.

    PubMed Central  CAS  PubMed  Google Scholar 

  159. de Hoon M, Hayashizaki Y. Deep cap analysis gene expression (CAGE): genome-wide identification of promoters, quantification of their expression, and network inference. Biotechniques. 2008;44(5):627–8. 630, 632, PM:18474037.

    PubMed  Google Scholar 

  160. Fullwood MJ, Ruan Y. ChIP-based methods for the identification of long-range chromatin interactions. J Cell Biochem. 2009;107(1):30–9. PM:19247990.

    PubMed Central  CAS  PubMed  Google Scholar 

  161. Crawford GE, Davis S, Scacheri PC, Renaud G, Halawi MJ, Erdos MR, et al. DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nat Methods. 2006;3(7):503–9. PM:16791207.

    PubMed Central  CAS  PubMed  Google Scholar 

  162. Giresi PG, Kim J, McDaniell RM, Iyer VR, Lieb JD. FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Res. 2007;17(6):877–85. PM:17179217.

    PubMed Central  CAS  PubMed  Google Scholar 

  163. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. 4.2 Chromosomal DNA and its packaging in the chromatin fiber. In: Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P, editors. Molecular biology of the cell. 4th ed. New York, NY: Garland Science; 2002. http://www.ncbi.nlm.nih.gov/books/NBK26834/.

    Google Scholar 

  164. Maeshima K, Imai R, Tamura S, Nozaki T. Chromatin as dynamic 10-nm fibers. Chromosoma. 2014;123(3):225–37. PM:24737122.

    PubMed Central  CAS  PubMed  Google Scholar 

  165. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705. PM:17320507.

    CAS  PubMed  Google Scholar 

  166. Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer. 2006;6(11):846–56. PM:17060944.

    CAS  PubMed  Google Scholar 

  167. Kouzarides T. SnapShot: histone-modifying enzymes. Cell. 2007;128(4):802. PM:17320515.

    CAS  PubMed  Google Scholar 

  168. Bronner C, Krifa M, Mousli M. Increasing role of UHRF1 in the reading and inheritance of the epigenetic code as well as in tumorogenesis. Biochem Pharmacol. 2013;86(12):1643–9. PM:24134914.

    CAS  PubMed  Google Scholar 

  169. Hake SB, Xiao A, Allis CD. Linking the epigenetic ‘language’ of covalent histone modifications to cancer. Br J Cancer. 2007;96(Suppl):R31–9. PM:17393583.

    PubMed  Google Scholar 

  170. Jin F, Li Y, Ren B, Natarajan R. Enhancers: multi-dimensional signal integrators. Transcription. 2011;2(5):226–30. PM:22231119.

    PubMed Central  CAS  PubMed  Google Scholar 

  171. Koch CM, Andrews RM, Flicek P, Dillon SC, Karaoz U, Clelland GK, et al. The landscape of histone modifications across 1 % of the human genome in five human cell lines. Genome Res. 2007;17(6):691–707. PM:17567990.

    PubMed Central  CAS  PubMed  Google Scholar 

  172. Simon JA, Kingston RE. Occupying chromatin: polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol Cell. 2013;49(5):808–24. PM:23473600.

    PubMed Central  CAS  PubMed  Google Scholar 

  173. Sarda S, Hannenhalli S. Next-generation sequencing and epigenomics research: a hammer in search of nails. Genomics Inform. 2014;12(1):2–11. PM:24748856.

    PubMed Central  PubMed  Google Scholar 

  174. Djebali S, Lagarde J, Kapranov P, Lacroix V, Borel C, Mudge JM, et al. Evidence for transcript networks composed of chimeric RNAs in human cells. PLoS One. 2012;7(1), e28213. PM:22238572.

    PubMed Central  CAS  PubMed  Google Scholar 

  175. Giacomini CP, Sun S, Varma S, Shain AH, Giacomini MM, Balagtas J, et al. Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types. PLoS Genet. 2013;9(4), e1003464. PM:23637631.

    PubMed Central  CAS  PubMed  Google Scholar 

  176. Greger L, Su J, Rung J, Ferreira PG, Lappalainen T, Dermitzakis ET, et al. Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants. PLoS One. 2014;9(8), e104567. PM:25133550.

    PubMed Central  PubMed  Google Scholar 

  177. Lappalainen T, Sammeth M, Friedlander MR, ’t Hoen PA, Monlong J, Rivas MA, et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature. 2013;501(7468):506–11. PM:24037378.

    PubMed Central  CAS  PubMed  Google Scholar 

  178. Guigo R, Valcarcel J. RNA. Prescribing splicing. Science. 2015;347(6218):124–5. PM:25574005.

    CAS  PubMed  Google Scholar 

  179. Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, et al. RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science. 2015;347(6218):1254806. PM:25525159.

    PubMed  Google Scholar 

  180. GENCODE Project Working Group. GENCODE Project. NHGRI, NIH and Wellcome Trust Sanger Institute. 2014. http://www.gencodegenes.org/stats.html.

  181. Mudge JM, Frankish A, Harrow J. Functional transcriptomics in the post-ENCODE era. Genome Res. 2013;23(12):1961–73. PM:24172201.

    PubMed Central  CAS  PubMed  Google Scholar 

  182. Atkinson SR, Marguerat S, Bahler J. Exploring long non-coding RNAs through sequencing. Semin Cell Dev Biol. 2012;23(2):200–5. PM:22202731.

    CAS  PubMed  Google Scholar 

  183. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307. PM:23498938.

    PubMed Central  CAS  PubMed  Google Scholar 

  184. Clerc P, Avner P. New lessons from random X-chromosome inactivation in the mouse. J Mol Biol. 2011;409(1):62–9. PM:21329697.

    CAS  PubMed  Google Scholar 

  185. Shi X, Sun M, Liu H, Yao Y, Song Y. Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett. 2013;339(2):159–66. PM:23791884.

    CAS  PubMed  Google Scholar 

  186. Rinn J, Guttman M. RNA Function. RNA and dynamic nuclear organization Science. 2014;345(6202):1240–1. PM:25214588.

    CAS  PubMed  Google Scholar 

  187. Derrien T, Guigo R, Johnson R. The Long Non-Coding RNAs: A New (P)layer in the “Dark Matter”. Front Genet. 2011;2:107. PM:22303401.

    PubMed Central  PubMed  Google Scholar 

  188. Wei W, Pelechano V, Jarvelin AI, Steinmetz LM. Functional consequences of bidirectional promoters. Trends Genet. 2011;27(7):267–76. PM:21601935.

    PubMed Central  CAS  PubMed  Google Scholar 

  189. De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK, et al. A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 2010;8(5), e1000384. PM:20485488.

    PubMed Central  PubMed  Google Scholar 

  190. Mousavi K, Zare H, Dell’orso S, Grontved L, Gutierrez-Cruz G, Derfoul A, et al. eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. Mol Cell. 2013;51(5):606–17. PM:23993744.

    PubMed Central  CAS  PubMed  Google Scholar 

  191. Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, et al. The regulated retrotransposon transcriptome of mammalian cells. Nat Genet. 2009;41(5):563–71. PM:19377475.

    CAS  PubMed  Google Scholar 

  192. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465(7301):1033–8. PM:20577206.

    PubMed Central  CAS  PubMed  Google Scholar 

  193. Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38(16):5366–83. PM:20423907.

    PubMed Central  CAS  PubMed  Google Scholar 

  194. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea MD, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–72. PM:19571010.

    PubMed Central  CAS  PubMed  Google Scholar 

  195. Hu G, Tang Q, Sharma S, Yu F, Escobar TM, Muljo SA, et al. Expression and regulation of intergenic long noncoding RNAs during T cell development and differentiation. Nat Immunol. 2013;14(11):1190–8. PM:24056746.

    PubMed Central  CAS  PubMed  Google Scholar 

  196. Gontan C, Achame EM, Demmers J, Barakat TS, Rentmeester E. van IW, et al. RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature. 2012;485(7398):386–90. PM:22596162.

    CAS  PubMed  Google Scholar 

  197. Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD, Qin YY, et al. Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer. 2014;13:156. PM:24953832.

    PubMed Central  PubMed  Google Scholar 

  198. Alam T, Medvedeva YA, Jia H, Brown JB, Lipovich L, Bajic VB. Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes. PLoS One. 2014;9(10), e109443. PM:25275320.

    PubMed Central  PubMed  Google Scholar 

  199. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell. 1999;97(1):17–27. PM:10199399.

    CAS  PubMed  Google Scholar 

  200. Yang L, Lin C, Jin C, Yang JC, Tanasa B, Li W, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature. 2013;500(7464):598–602. PM:23945587.

    PubMed Central  CAS  PubMed  Google Scholar 

  201. Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol. 2007;3(3):166–73. PM:17259978.

    CAS  PubMed  Google Scholar 

  202. Chu Y, Yue X, Younger ST, Janowski BA, Corey DR. Involvement of argonaute proteins in gene silencing and activation by RNAs complementary to a non-coding transcript at the progesterone receptor promoter. Nucleic Acids Res. 2010;38(21):7736–48. PM:20675357.

    PubMed Central  CAS  PubMed  Google Scholar 

  203. Wang J, Zhuang J, Iyer S, Lin X, Whitfield TW, Greven MC, et al. Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res. 2012;22(9):1798–812. PM:22955990.

    PubMed Central  CAS  PubMed  Google Scholar 

  204. Sun BK, Deaton AM, Lee JT. A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell. 2006;21(5):617–28. PM:16507360.

    CAS  PubMed  Google Scholar 

  205. Hesselberth JR, Chen X, Zhang Z, Sabo PJ, Sandstrom R, Reynolds AP, et al. Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat Methods. 2009;6(4):283–9. PM:19305407.

    PubMed Central  CAS  PubMed  Google Scholar 

  206. Hoffman MM, Ernst J, Wilder SP, Kundaje A, Harris RS, Libbrecht M, et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2013;41(2):827–41. PM:23221638.

    PubMed Central  CAS  PubMed  Google Scholar 

  207. Wikipedia. Hidden Markov model. Wikipedia. 2014. http://en.wikipedia.org/wiki/Hidden_Markov_model.

  208. Stamp M. A revealing introduction to hidden markov models. Mark Stamp, Professor, Department of Computer Science, San Jose State University. 2012. http://www.cs.sjsu.edu/~stamp/RUA/HMM.pdf.

  209. Eddy SR. What is a hidden Markov model? Nat Biotechnol. 2004;22(10):1315–6. PM:15470472.

    CAS  PubMed  Google Scholar 

  210. Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, et al. Comparative analysis of metazoan chromatin organization. Nature. 2014;512(7515):449–52. PM:25164756.

    PubMed Central  CAS  PubMed  Google Scholar 

  211. Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, et al. TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res. 2006;34(Database issue):D108–10. PM:16381825.

    PubMed Central  CAS  PubMed  Google Scholar 

  212. Wingender E, Dietze P, Karas H, Knuppel R. TRANSFAC: a database on transcription factors and their DNA binding sites. Nucleic Acids Res. 1996;24(1):238–41. PM:8594589.

    PubMed Central  CAS  PubMed  Google Scholar 

  213. Bryne JC, Valen E, Tang MH, Marstrand T, Winther O. da P, I, et al. JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update. Nucleic Acids Res. 2008;36(Database issue):D102–6. PM:18006571.

    PubMed Central  CAS  PubMed  Google Scholar 

  214. Newburger DE, Bulyk ML. UniPROBE: an online database of protein binding microarray data on protein-DNA interactions. Nucleic Acids Res. 2009;37(Database issue):D77–82. PM:18842628.

    PubMed Central  CAS  PubMed  Google Scholar 

  215. Alon U. An introduction to systems biology: design principles of biological circuits. 1st ed. Boca Raton, FL: Chapman and Hall/CRC; 2006. Fl 33487–2742.

    Google Scholar 

  216. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Organelles of the Eukaryotic cell. In: Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J, editors. Molecular cell biology. 4th ed. New York, NY: W H Freeman; 2000. http://www.ncbi.nlm.nih.gov/books/NBK21743/.

    Google Scholar 

  217. Cooper GM. 1.1 The origin and evolution of cells. In: Cooper GM, editor. The cell: a molecular approach. 2nd ed. Sunderland, MA: Sinauer Associates; 2000. http://www.ncbi.nlm.nih.gov/books/NBK9841/.

    Google Scholar 

  218. Dechat T, Adam SA, Taimen P, Shimi T, Goldman RD. Nuclear lamins. Cold Spring Harb Perspect Biol. 2010;2(11):a000547. PM:20826548.

    PubMed Central  CAS  PubMed  Google Scholar 

  219. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, et al. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008;453(7197):948–51. PM:18463634.

    CAS  PubMed  Google Scholar 

  220. Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, Brugman W, et al. Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell. 2010;38(4):603–13. PM:20513434.

    CAS  PubMed  Google Scholar 

  221. Kaiser TE, Intine RV, Dundr M. De novo formation of a subnuclear body. Science. 2008;322(5908):1713–7. PM:18948503.

    CAS  PubMed  Google Scholar 

  222. Spector DL, Lamond AI. Nuclear speckles. Cold Spring Harb Perspect Biol. 2011;3(2), PM:20926517.

    Google Scholar 

  223. Rieder D, Trajanoski Z, McNally JG. Transcription factories. Front Genet. 2012;3:221. PM:23109938.

    PubMed Central  PubMed  Google Scholar 

  224. Langston LD, Indiani C, O’Donnell M. Whither the replisome: emerging perspectives on the dynamic nature of the DNA replication machinery. Cell Cycle. 2009;8(17):2686–91. PM:19652539.

    PubMed Central  CAS  PubMed  Google Scholar 

  225. Belin BJ, Mullins RD. What we talk about when we talk about nuclear actin. Nucleus. 2013;4(4):291–7. PM:23934079.

    PubMed Central  PubMed  Google Scholar 

  226. Belin BJ, Cimini BA, Blackburn EH, Mullins RD. Visualization of actin filaments and monomers in somatic cell nuclei. Mol Biol Cell. 2013;24(7):982–94. PM:23447706.

    PubMed Central  CAS  PubMed  Google Scholar 

  227. Nickerson JA, Krockmalnic G, Wan KM, Penman S. The nuclear matrix revealed by eluting chromatin from a cross-linked nucleus. Proc Natl Acad Sci U S A. 1997;94(9):4446–50. PM:9114009.

    PubMed Central  CAS  PubMed  Google Scholar 

  228. Nickerson J. Experimental observations of a nuclear matrix. J Cell Sci. 2001;114(Pt 3):463–74. PM:11171316.

    CAS  PubMed  Google Scholar 

  229. Pederson T. Half a century of “the nuclear matrix”. Mol Biol Cell. 2000;11(3):799–805. PM:10712500.

    PubMed Central  CAS  PubMed  Google Scholar 

  230. Pederson T. The nucleus introduced. Cold Spring Harb Perspect Biol. 2011;3(5), PM:20660024.

    Google Scholar 

  231. Pederson T. The nuclear physique. Int Rev Cell Mol Biol. 2014;307:1–13. PM:24380590.

    PubMed  Google Scholar 

  232. Wilson RH, Coverley D. Relationship between DNA replication and the nuclear matrix. Genes Cells. 2013;18(1):17–31. PM:23134523.

    PubMed Central  CAS  PubMed  Google Scholar 

  233. Albrethsen J, Knol JC, Jimenez CR. Unravelling the nuclear matrix proteome. J Proteomics. 2009;72(1):71–81. PM:18957335.

    CAS  PubMed  Google Scholar 

  234. Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, et al. The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev. 2008;22(24):3409–21. PM:19141474.

    PubMed Central  CAS  PubMed  Google Scholar 

  235. Mandelkern M, Elias JG, Eden D, Crothers DM. The dimensions of DNA in solution. J Mol Biol. 1981;152(1):153–61. PM:7338906.

    CAS  PubMed  Google Scholar 

  236. Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, et al. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol. 2005;3(5), e157. PM:15839726.

    PubMed Central  PubMed  Google Scholar 

  237. Cremer T, Cremer M. Chromosome territories. Cold Spring Harb Perspect Biol. 2010;2(3):a003889. PM:20300217.

    PubMed Central  PubMed  Google Scholar 

  238. Rouquette J, Cremer C, Cremer T, Fakan S. Functional nuclear architecture studied by microscopy: present and future. Int Rev Cell Mol Biol. 2010;282:1–90. PM:20630466.

    CAS  PubMed  Google Scholar 

  239. Cvackova Z, Masata M, Stanek D, Fidlerova H, Raska I. Chromatin position in human HepG2 cells: although being non-random, significantly changed in daughter cells. J Struct Biol. 2009;165(2):107–17. PM:19056497.

    PubMed Central  CAS  PubMed  Google Scholar 

  240. Mehta IS, Amira M, Harvey AJ, Bridger JM. Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts. Genome Biol. 2010;11(1):R5. PM:20070886.

    PubMed Central  PubMed  Google Scholar 

  241. Markaki Y, Gunkel M, Schermelleh L, Beichmanis S, Neumann J, Heidemann M, et al. Functional nuclear organization of transcription and DNA replication: a topographical marriage between chromatin domains and the interchromatin compartment. Cold Spring Harb Symp Quant Biol. 2010;75:475–92. PM:21467142.

    CAS  PubMed  Google Scholar 

  242. Bartova E, Kozubek S. Nuclear architecture in the light of gene expression and cell differentiation studies. Biol Cell. 2006;98(6):323–36. PM:16704376.

    CAS  PubMed  Google Scholar 

  243. Solovei I, Kreysing M, Lanctot C, Kosem S, Peichl L, Cremer T, et al. Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell. 2009;137(2):356–68. PM:19379699.

    CAS  PubMed  Google Scholar 

  244. Ma H, Samarabandu J, Devdhar RS, Acharya R, Cheng PC, Meng C, et al. Spatial and temporal dynamics of DNA replication sites in mammalian cells. J Cell Biol. 1998;143(6):1415–25. PM:9852140.

    PubMed Central  CAS  PubMed  Google Scholar 

  245. Jackson DA, Pombo A. Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J Cell Biol. 1998;140(6):1285–95. PM:9508763.

    PubMed Central  CAS  PubMed  Google Scholar 

  246. Albiez H, Cremer M, Tiberi C, Vecchio L, Schermelleh L, Dittrich S, et al. Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks. Chromosome Res. 2006;14(7):707–33. PM:17115328.

    CAS  PubMed  Google Scholar 

  247. Kolbl AC, Weigl D, Mulaw M, Thormeyer T, Bohlander SK, Cremer T, et al. The radial nuclear positioning of genes correlates with features of megabase-sized chromatin domains. Chromosome Res. 2012;20(6):735–52. PM:23053570.

    PubMed  Google Scholar 

  248. Huet S, Lavelle C, Ranchon H, Carrivain P, Victor JM, Bancaud A. Relevance and limitations of crowding, fractal, and polymer models to describe nuclear architecture. Int Rev Cell Mol Biol. 2014;307:443–79. PM:24380602.

    CAS  PubMed  Google Scholar 

  249. Hirano T. At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol. 2006;7(5):311–22. PM:16633335.

    CAS  PubMed  Google Scholar 

  250. Thadani R, Uhlmann F, Heeger S. Condensin, chromatin crossbarring and chromosome condensation. Curr Biol. 2012;22(23):R1012–21. PM:23218009.

    CAS  PubMed  Google Scholar 

  251. Takahashi M. A fractal model of chromosomes and chromosomal DNA replication. J Theor Biol. 1989;141(1):117–36. PM:2699341.

    CAS  PubMed  Google Scholar 

  252. Lieberman-Aiden E, van Berkum NL, 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(5950):289–93. PM:19815776.

    PubMed Central  CAS  PubMed  Google Scholar 

  253. Schermelleh L, Heintzmann R, Leonhardt H. A guide to super-resolution fluorescence microscopy. J Cell Biol. 2010;190(2):165–75. PM:20643879.

    PubMed Central  CAS  PubMed  Google Scholar 

  254. Schermelleh L, Carlton PM, Haase S, Shao L, Winoto L, Kner P, et al. Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy. Science. 2008;320(5881):1332–6. PM:18535242.

    PubMed Central  CAS  PubMed  Google Scholar 

  255. Cremer C, Masters BR. Resolution enhancement techniques in microscopy. Eur Phys J H. 2013;38:281–344. http://dx.doi.org/10.1140/epjh/e2012-20060-1.

    Google Scholar 

  256. de Laat W, Dekker J. 3C-based technologies to study the shape of the genome. Methods. 2012;58(3):189–91. PM:23199640.

    PubMed  Google Scholar 

  257. de Wit E. de LW. A decade of 3C technologies: insights into nuclear organization. Genes Dev. 2012;26(1):11–24. PM:22215806.

    PubMed Central  PubMed  Google Scholar 

  258. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science. 2002;295(5558):1306–11. PM:11847345.

    CAS  PubMed  Google Scholar 

  259. Lieberman-Aiden E. Zoom! Science. 2009;334:1222–3. http://www.sciencemag.org/content/334/6060/1222.long.

    Google Scholar 

  260. Bickmore WA, van Steensel B. Genome architecture: domain organization of interphase chromosomes. Cell. 2013;152(6):1270–84. PM:23498936.

    CAS  PubMed  Google Scholar 

  261. Gibcus JH, Dekker J. The hierarchy of the 3D genome. Mol Cell. 2013;49(5):773–82. PM:23473598.

    PubMed Central  CAS  PubMed  Google Scholar 

  262. Naumova N, Smith EM, Zhan Y, Dekker J. Analysis of long-range chromatin interactions using chromosome conformation capture. Methods. 2012;58(3):192–203. PM:22903059.

    CAS  PubMed  Google Scholar 

  263. Hakim O, Sung MH, Voss TC, Splinter E, John S, Sabo PJ, et al. Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements. Genome Res. 2011;21(5):697–706. PM:21471403.

    PubMed Central  CAS  PubMed  Google Scholar 

  264. Dostie J, Richmond TA, Arnaout RA, Selzer RR, Lee WL, Honan TA, et al. Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res. 2006;16(10):1299–309. PM:16954542.

    PubMed Central  CAS  PubMed  Google Scholar 

  265. 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;485(7398):376–80. PM:22495300.

    PubMed Central  CAS  PubMed  Google Scholar 

  266. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N, et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature. 2012;485(7398):381–5. PM:22495304.

    PubMed Central  CAS  PubMed  Google Scholar 

  267. 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(3):458–72. PM:22265598.

    CAS  PubMed  Google Scholar 

  268. Zhang Y, McCord RP, Ho YJ, Lajoie BR, Hildebrand DG, Simon AC, et al. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell. 2012;148(5):908–21. PM:22341456.

    PubMed Central  CAS  PubMed  Google Scholar 

  269. Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014;159(7):1665–80. PM:25497547.

    CAS  PubMed  Google Scholar 

  270. Collins F. Cool videos: know when to fold them. NIH Directors Blog—National Institutes of Health (USA). 2014. http://directorsblog.nih.gov/2014/12/11/cool-videos-know-when-to-fold-them/#more-4024.

  271. de Graaf CA, van Steensel B. Chromatin organization: form to function. Curr Opin Genet Dev. 2013;23(2):185–90. PM:23274160.

    PubMed  Google Scholar 

  272. Hou C, Li L, Qin ZS, Corces VG. Gene density, transcription, and insulators contribute to the partition of the Drosophila genome into physical domains. Mol Cell. 2012;48(3):471–84. PM:23041285.

    PubMed Central  CAS  PubMed  Google Scholar 

  273. Phillips-Cremins JE, Corces VG. Chromatin insulators: linking genome organization to cellular function. Mol Cell. 2013;50(4):461–74. PM:23706817.

    PubMed Central  CAS  PubMed  Google Scholar 

  274. Phillips-Cremins JE. Unraveling architecture of the pluripotent genome. Curr Opin Cell Biol. 2014;28:96–104. PM:24813689.

    CAS  PubMed  Google Scholar 

  275. Hakim O, Sung MH, Nakayamada S, Voss TC, Baek S, Hager GL. Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation. Genome Res. 2013;23(3):462–72. PM:23212947.

    PubMed Central  CAS  PubMed  Google Scholar 

  276. Melo CA, Drost J, Wijchers PJ, van de Werken H, de Wit E, Oude Vrielink JA, et al. eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell. 2013;49(3):524–35. PM:23273978.

    CAS  PubMed  Google Scholar 

  277. Eijkelenboom A, Mokry M. de WE, Smits LM, Polderman PE, van Triest MH, et al. Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling. Mol Syst Biol. 2013;9:638. PM:23340844.

    PubMed Central  PubMed  Google Scholar 

  278. Inbar-Feigenberg M, Choufani S, Butcher DT, Roifman M, Weksberg R. Basic concepts of epigenetics. Fertil Steril. 2013;99(3):607–15. PM:23357459.

    CAS  PubMed  Google Scholar 

  279. Maunakea AK, Chepelev I, Zhao K. Epigenome mapping in normal and disease States. Circ Res. 2010;107(3):327–39. PM:20689072.

    PubMed Central  CAS  PubMed  Google Scholar 

  280. Klose RJ, Cooper S, Farcas AM, Blackledge NP, Brockdorff N. Chromatin sampling: an emerging perspective on targeting polycomb repressor proteins. PLoS Genet. 2013;9(8), e1003717. PM:23990804.

    PubMed Central  CAS  PubMed  Google Scholar 

  281. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 2006;125(2):301–13. PM:16630818.

    PubMed Central  CAS  PubMed  Google Scholar 

  282. Cheutin T, Cavalli G. Polycomb silencing: from linear chromatin domains to 3D chromosome folding. Curr Opin Genet Dev. 2014;25:30–7. PM:24434548.

    CAS  PubMed  Google Scholar 

  283. Saurin AJ, Shiels C, Williamson J, Satijn DP, Otte AP, Sheer D, et al. The human polycomb group complex associates with pericentromeric heterochromatin to form a novel nuclear domain. J Cell Biol. 1998;142(4):887–98. PM:9722603.

    PubMed Central  CAS  PubMed  Google Scholar 

  284. Lund AH, van Lohuizen M. Polycomb complexes and silencing mechanisms. Curr Opin Cell Biol. 2004;16(3):239–46. PM:15145347.

    CAS  PubMed  Google Scholar 

  285. Koziol MJ, Rinn JL. RNA traffic control of chromatin complexes. Curr Opin Genet Dev. 2010;20(2):142–8. PM:20362426.

    PubMed Central  CAS  PubMed  Google Scholar 

  286. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322(5902):750–6. PM:18974356.

    PubMed Central  CAS  PubMed  Google Scholar 

  287. Gardner KE, Allis CD, Strahl BD. Operating on chromatin, a colorful language where context matters. J Mol Biol. 2011;409(1):36–46. PM:21272588.

    PubMed Central  CAS  PubMed  Google Scholar 

  288. Sauvageau M, Goff LA, Lodato S, Bonev B, Groff AF, Gerhardinger C, et al. Multiple knockout mouse models reveal lincRNAs are required for life and brain development. Elife. 2013;2, e01749. PM:24381249.

    PubMed Central  PubMed  Google Scholar 

  289. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19. PM:20673990.

    PubMed Central  CAS  PubMed  Google Scholar 

  290. Chu C, Quinn J, Chang HY. Chromatin isolation by RNA purification (ChIRP). J Vis Exp. 2012;61. PM:22472705.

    Google Scholar 

  291. Simon MD, Wang CI, Kharchenko PV, West JA, Chapman BA, Alekseyenko AA, et al. The genomic binding sites of a noncoding RNA. Proc Natl Acad Sci U S A. 2011;108(51):20497–502. PM:22143764.

    PubMed Central  CAS  PubMed  Google Scholar 

  292. Simon MD. Capture hybridization analysis of RNA targets (CHART). Curr Protoc Mol Biol. 2013;Chapter 21:Unit, PM:23288463

    Google Scholar 

  293. Mariner PD, Walters RD, Espinoza CA, Drullinger LF, Wagner SD, Kugel JF, et al. Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol Cell. 2008;29(4):499–509. PM:18313387.

    CAS  PubMed  Google Scholar 

  294. Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C, et al. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science. 2013;341(6147):1237973. PM:23828888.

    PubMed Central  PubMed  Google Scholar 

  295. Li L, Liu B, Wapinski OL, Tsai MC, Qu K, Zhang J, et al. Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Rep. 2013;5(1):3–12. PM:24075995.

    PubMed Central  CAS  PubMed  Google Scholar 

  296. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6. PM:20393566.

    PubMed Central  CAS  PubMed  Google Scholar 

  297. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329(5992):689–93. PM:20616235.

    PubMed Central  CAS  PubMed  Google Scholar 

  298. Dasen JS. Long noncoding RNAs in development: solidifying the Lncs to Hox gene regulation. Cell Rep. 2013;5(1):1–2. PM:24139230.

    CAS  PubMed  Google Scholar 

  299. Chu C, Qu K, Zhong FL, Artandi SE, Chang HY. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell. 2011;44(4):667–78. PM:21963238.

    PubMed Central  CAS  PubMed  Google Scholar 

  300. Woo CJ, Kharchenko PV, Daheron L, Park PJ, Kingston RE. A region of the human HOXD cluster that confers polycomb-group responsiveness. Cell. 2010;140(1):99–110. PM:20085705.

    PubMed Central  CAS  PubMed  Google Scholar 

  301. Sing A, Pannell D, Karaiskakis A, Sturgeon K, Djabali M, Ellis J, et al. A vertebrate polycomb response element governs segmentation of the posterior hindbrain. Cell. 2009;138(5):885–97. PM:19737517.

    CAS  PubMed  Google Scholar 

  302. GeneLoc. NEAT1 gene. GeneCardsPlus. 2014. http://www.genecards.org/cgi-bin/carddisp.pl?gene = NEAT1#genomic_location.

  303. Shevtsov SP, Dundr M. Nucleation of nuclear bodies by RNA. Nat Cell Biol. 2011;13(2):167–73. PM:21240286.

    CAS  PubMed  Google Scholar 

  304. Mao YS, Sunwoo H, Zhang B, Spector DL. Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol. 2011;13(1):95–101. PM:21170033.

    PubMed Central  CAS  PubMed  Google Scholar 

  305. Quinodoz S, Guttman M. Long noncoding RNAs: an emerging link between gene regulation and nuclear organization. Trends Cell Biol. 2014;24(11):651–63. https://www-clinicalkey-com.proxy.library.vcu.edu/#!/content/playContent/1-s2.0-S0962892414001469.

    CAS  PubMed  Google Scholar 

  306. Choudhry H, Albukhari A, Morotti M, Hider S, Moralli D, Smythies J, et al. Tumor hypoxia induces nuclear paraspeckle formation through HIF-2alpha dependent transcriptional activation of NEAT1 leading to cancer cell survival. Oncogene. 2014, PM:25417700.

    Google Scholar 

  307. Csankovszki G, Nagy A, Jaenisch R. Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol. 2001;153(4):773–84. PM:11352938.

    PubMed Central  CAS  PubMed  Google Scholar 

  308. Trojer P, Reinberg D. Facultative heterochromatin: is there a distinctive molecular signature? Mol Cell. 2007;28(1):1–13. PM:17936700.

    CAS  PubMed  Google Scholar 

  309. Lee JT. Gracefully ageing at 50, X-chromosome inactivation becomes a paradigm for RNA and chromatin control. Nat Rev Mol Cell Biol. 2011;12(12):815–26. PM:22108600.

    CAS  PubMed  Google Scholar 

  310. Jeon Y, Sarma K, Lee JT. New and Xisting regulatory mechanisms of X chromosome inactivation. Curr Opin Genet Dev. 2012;22(2):62–71. PM:22424802.

    PubMed Central  CAS  PubMed  Google Scholar 

  311. Pinter SF, Sadreyev RI, Yildirim E, Jeon Y, Ohsumi TK, Borowsky M, et al. Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations. Genome Res. 2012;22(10):1864–76. PM:22948768.

    PubMed Central  CAS  PubMed  Google Scholar 

  312. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N. Requirement for Xist in X chromosome inactivation. Nature. 1996;379(6561):131–7. PM:8538762.

    CAS  PubMed  Google Scholar 

  313. Marahrens Y, Panning B, Dausman J, Strauss W, Jaenisch R. Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev. 1997;11(2):156–66. PM:9009199.

    CAS  PubMed  Google Scholar 

  314. Pageau GJ, Hall LL, Ganesan S, Livingston DM, Lawrence JB. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer. 2007;7(8):628–33. PM:17611545.

    CAS  PubMed  Google Scholar 

  315. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, et al. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell. 2013;152(4):727–42. PM:23415223.

    CAS  PubMed  Google Scholar 

  316. GeneLoc. X inactivation center. GeneCardsPlus. 2014. http://www.genecards.org/cgi-bin/carddisp.pl?gene = XIC&search = 466fb42146015538a26a23c7008d81a7.

  317. Brown CJ, Hendrich BD, Rupert JL, Lafreniere RG, Xing Y, Lawrence J, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71(3):527–42. PM:1423611.

    CAS  PubMed  Google Scholar 

  318. Brown CJ, Carrel L, Willard HF. Expression of genes from the human active and inactive X chromosomes. Am J Hum Genet. 1997;60(6):1333–43. PM:9199554.

    PubMed Central  CAS  PubMed  Google Scholar 

  319. Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. 2008;320(5881):1336–41. PM:18535243.

    PubMed Central  CAS  PubMed  Google Scholar 

  320. Clemson CM, McNeil JA, Willard HF, Lawrence JB. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol. 1996;132(3):259–75. PM:8636206.

    CAS  PubMed  Google Scholar 

  321. Chaumeil J, Le BP, Wutz A, Heard E. A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes Dev. 2006;20(16):2223–37. PM:16912274.

    PubMed Central  CAS  PubMed  Google Scholar 

  322. Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S. The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev Cell. 2010;19(3):469–76. PM:20833368.

    CAS  PubMed  Google Scholar 

  323. Gohring F, Fackelmayer FO. The scaffold/matrix attachment region binding protein hnRNP-U (SAF-A) is directly bound to chromosomal DNA in vivo: a chemical cross-linking study. Biochemistry. 1997;36(27):8276–83. PM:9204873.

    CAS  PubMed  Google Scholar 

  324. Wutz A, Rasmussen TP, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet. 2002;30(2):167–74. PM:11780141.

    CAS  PubMed  Google Scholar 

  325. Csankovszki G, Panning B, Bates B, Pehrson JR, Jaenisch R. Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation. Nat Genet. 1999;22(4):323–4. PM:10431231.

    CAS  PubMed  Google Scholar 

  326. Brown CJ, Willard HF. The human X-inactivation centre is not required for maintenance of X-chromosome inactivation. Nature. 1994;368(6467):154–6. PM:8139659.

    CAS  PubMed  Google Scholar 

  327. Silva J, Mak W, Zvetkova I, Appanah R, Nesterova TB, Webster Z, et al. Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell. 2003;4(4):481–95. PM:12689588.

    CAS  PubMed  Google Scholar 

  328. Plath K, Talbot D, Hamer KM, Otte AP, Yang TP, Jaenisch R, et al. Developmentally regulated alterations in Polycomb repressive complex 1 proteins on the inactive X chromosome. J Cell Biol. 2004;167(6):1025–35. PM:15596546.

    PubMed Central  CAS  PubMed  Google Scholar 

  329. Nozawa RS, Nagao K, Igami KT, Shibata S, Shirai N, Nozaki N, et al. Human inactive X chromosome is compacted through a PRC2-independent SMCHD1-HBiX1 pathway. Nat Struct Mol Biol. 2013;20(5):566–73. PM:23542155.

    CAS  PubMed  Google Scholar 

  330. Simon MD, Pinter SF, Fang R, Sarma K, Rutenberg-Schoenberg M, Bowman SK, et al. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature. 2013;504(7480):465–9. PM:24162848.

    PubMed Central  CAS  PubMed  Google Scholar 

  331. Clemson CM, Chow JC, Brown CJ, Lawrence JB. Stabilization and localization of Xist RNA are controlled by separate mechanisms and are not sufficient for X inactivation. J Cell Biol. 1998;142(1):13–23. PM:9660859.

    PubMed Central  CAS  PubMed  Google Scholar 

  332. Hansen RS, Canfield TK, Stanek AM, Keitges EA, Gartler SM. Reactivation of XIST in normal fibroblasts and a somatic cell hybrid: abnormal localization of XIST RNA in hybrid cells. Proc Natl Acad Sci U S A. 1998;95(9):5133–8. PM:9560241.

    PubMed Central  CAS  PubMed  Google Scholar 

  333. Zhang LF, Huynh KD, Lee JT. Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell. 2007;129(4):693–706. PM:17512404.

    CAS  PubMed  Google Scholar 

  334. GeneLoc. Functional intergenic repeating RNA element (Firre) gene. GeneCardsPlus. 2014. http://www.genecards.org/cgi-bin/carddisp.pl?gene=FIRRE&search=f233f368d11de075737fc5d2d196ea55.

  335. Sun L, Goff LA, Trapnell C, Alexander R, Lo KA, Hacisuleyman E, et al. Long noncoding RNAs regulate adipogenesis. Proc Natl Acad Sci U S A. 2013;110(9):3387–92. PM:23401553.

    PubMed Central  CAS  PubMed  Google Scholar 

  336. Hacisuleyman E, Goff LA, Trapnell C, Williams A, Henao-Mejia J, Sun L, et al. Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nat Struct Mol Biol. 2014;21(2):198–206. PM:24463464.

    PubMed Central  CAS  PubMed  Google Scholar 

  337. Nukitrangsan N, Okabe T, Toda T, Inafuku M, Iwasaki H, Yanagita T, et al. Effect of Peucedanum japonicum Thunb on the expression of obesity-related genes in mice on a high-fat diet. J Oleo Sci. 2011;60(10):527–36. PM:21937852.

    CAS  PubMed  Google Scholar 

  338. Rubi B. Pyridoxal 5′-phosphate (PLP) deficiency might contribute to the onset of type I diabetes. Med Hypotheses. 2012;78(1):179–82. PM:22088923.

    CAS  PubMed  Google Scholar 

  339. Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, et al. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol Cell Biol. 2011;31(4):626–38. PM:21135128.

    PubMed Central  CAS  PubMed  Google Scholar 

  340. Seo J, Fortuno III ES, Suh JM, Stenesen D, Tang W, Parks EJ, et al. Atf4 regulates obesity, glucose homeostasis, and energy expenditure. Diabetes. 2009;58(11):2565–73. PM:19690063.

    PubMed Central  CAS  PubMed  Google Scholar 

  341. Choy L, Derynck R. Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J Biol Chem. 2003;278(11):9609–19. PM:12524424.

    CAS  PubMed  Google Scholar 

  342. Zhang Q, Yu N, Lee C. Mysteries of TGF-beta paradox in benign and malignant cells. Front Oncol. 2014;4:94. PM:24860782.

    PubMed Central  PubMed  Google Scholar 

  343. Sarge KD, Park-Sarge OK. Mitotic bookmarking of formerly active genes: keeping epigenetic memories from fading. Cell Cycle. 2009;8(6):818–23. PM:19221503.

    PubMed Central  CAS  PubMed  Google Scholar 

  344. Kadauke S, Udugama MI, Pawlicki JM, Achtman JC, Jain DP, Cheng Y, et al. Tissue-specific mitotic bookmarking by hematopoietic transcription factor GATA1. Cell. 2012;150(4):725–37. PM:22901805.

    PubMed Central  CAS  PubMed  Google Scholar 

  345. Lake RJ, Tsai PF, Choi I, Won KJ, Fan HY. RBPJ, the major transcriptional effector of Notch signaling, remains associated with chromatin throughout mitosis, suggesting a role in mitotic bookmarking. PLoS Genet. 2014;10(3), e1004204. PM:24603501.

    PubMed Central  PubMed  Google Scholar 

  346. Wong MM, Byun JS, Sacta M, Jin Q, Baek S, Gardner K. Promoter-bound p300 complexes facilitate post-mitotic transmission of transcriptional memory. PLoS One. 2014;9(6), e99989. PM:24945803.

    PubMed Central  PubMed  Google Scholar 

  347. Zaidi SK, Grandy RA, Lopez-Camacho C, Montecino M, van Wijnen AJ, Lian JB, et al. Bookmarking target genes in mitosis: a shared epigenetic trait of phenotypic transcription factors and oncogenes? Cancer Res. 2014;74(2):420–5. PM:24408924.

    PubMed Central  CAS  PubMed  Google Scholar 

  348. Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS. Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol Cell. 2002;9(2):279–89. PM:11864602.

    CAS  PubMed  Google Scholar 

  349. Caravaca JM, Donahue G, Becker JS, He X, Vinson C, Zaret KS. Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes. Genes Dev. 2013;27(3):251–60. PM:23355396.

    PubMed Central  CAS  PubMed  Google Scholar 

  350. Yan J, Enge M, Whitington T, Dave K, Liu J, Sur I, et al. Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. Cell. 2013;154(4):801–13. PM:23953112.

    CAS  PubMed  Google Scholar 

  351. Rada-Iglesias A. Pioneering barren land: mitotic bookmarking by transcription factors. Dev Cell. 2013;24(4):342–4. PM:23449470.

    CAS  PubMed  Google Scholar 

  352. Apostolou E, Ferrari F, Walsh RM, Bar-Nur O, Stadtfeld M, Cheloufi S, et al. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. Cell Stem Cell. 2013;12(6):699–712. PM:23665121.

    PubMed Central  CAS  PubMed  Google Scholar 

  353. Zhang H, Jiao W, Sun L, Fan J, Chen M, Wang H, et al. Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming. Cell Stem Cell. 2013;13(1):30–5. PM:23747202.

    CAS  PubMed  Google Scholar 

  354. Sims D, Sudbery I, Ilott NE, Heger A, Ponting CP. Sequencing depth and coverage: key considerations in genomic analyses. Nat Rev Genet. 2014;15(2):121–32. PM:24434847.

    CAS  PubMed  Google Scholar 

  355. ENCODE Consortium. Experiment guidelines. ENCODE Consortium. 2014. https://www.encodeproject.org/about/experiment-guidelines/.

  356. ENCODE Consortium. Encode portal: getting started. ENCODE Consortium. 2014. https://www.encodeproject.org/help/getting-started.

  357. NCBI. Epigenomics help [internet]. National Center for Biotechnology Information. 2014. http://www.ncbi.nlm.nih.gov/books/NBK45786/#epi_help_doc.How_to_Use_the_Sample_Brows.

  358. Pastrello C, Pasini E, Kotlyar M, Otasek D, Wong S, Sangrar W, et al. Integration, visualization and analysis of human interactome. Biochem Biophys Res Commun. 2014;445(4):757–73. PM:24491561.

    CAS  PubMed  Google Scholar 

  359. Greene CS, Tan J, Ung M, Moore JH, Cheng C. Big data bioinformatics. J Cell Physiol. 2014;229(12):1896–900. PM:24799088.

    CAS  PubMed  Google Scholar 

  360. Sedaghat N, Saegusa T, Randolph T, Shojaie A. Comparative study of computational methods for reconstructing genetic networks of cancer-related pathways. Cancer Inform. 2014;13 Suppl 2:55–66. PM:25288880.

    PubMed Central  CAS  PubMed  Google Scholar 

  361. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz Jr LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546–58. PM:23539594.

    PubMed Central  CAS  PubMed  Google Scholar 

  362. Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res. 2014;42(Database issue):D199–205. PM:24214961.

    PubMed Central  CAS  PubMed  Google Scholar 

  363. Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 2012;40(Database issue):D109–14. PM:22080510.

    PubMed Central  CAS  PubMed  Google Scholar 

  364. Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2010;38(Database issue):D355–60. PM:19880382.

    PubMed Central  CAS  PubMed  Google Scholar 

  365. BioCarta.co. BioCarta Pathways. BioCarta com. 2014. http://www.biocarta.com/support/howto/path.asp.

  366. Croft D, O’Kelly G, Wu G, Haw R, Gillespie M, Matthews L, et al. Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res. 2011;39(Database issue):D691–7. PM:21067998.

    PubMed Central  CAS  PubMed  Google Scholar 

  367. Croft D, Mundo AF, Haw R, Milacic M, Weiser J, Wu G, et al. The Reactome pathway knowledgebase. Nucleic Acids Res. 2014;42(Database issue):D472–7. PM:24243840.

    PubMed Central  CAS  PubMed  Google Scholar 

  368. Cerami EG, Gross BE, Demir E, Rodchenkov I, Babur O, Anwar N, et al. Pathway commons, a web resource for biological pathway data. Nucleic Acids Res. 2011;39(Database issue):D685–90. PM:21071392.

    PubMed Central  CAS  PubMed  Google Scholar 

  369. Fernandez-Suarez XM, Rigden DJ, Galperin MY. The 2014 Nucleic Acids research database issue and an updated NAR online molecular biology database collection. Nucleic Acids Res. 2014;42(Database issue):D1–6. PM:24316579.

    PubMed Central  CAS  PubMed  Google Scholar 

  370. Good BM, Ainscough BJ, McMichael JF, Su AI, Griffith OL. Organizing knowledge to enable personalization of medicine in cancer. Genome Biol. 2014;15(8):438. PM:25222080.

    PubMed Central  PubMed  Google Scholar 

  371. Ong FS, Deignan JL, Kuo JZ, Bernstein KE, Rotter JI, Grody WW, et al. Clinical utility of pharmacogenetic biomarkers in cardiovascular therapeutics: a challenge for clinical implementation. Pharmacogenomics. 2012;13(4):465–75. PM:22380001.

    PubMed Central  CAS  PubMed  Google Scholar 

  372. Ong FS, Das K, Wang J, Vakil H, Kuo JZ, Blackwell WL, et al. Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing. Expert Rev Mol Diagn. 2012;12(6):593–602. PM:22845480.

    PubMed Central  CAS  PubMed  Google Scholar 

  373. Fan YS. Companion diagnostic testing for targeted cancer therapies: an overview. Genet Test Mol Biomarkers. 2013;17(7):515–23. PM:23574530.

    CAS  PubMed  Google Scholar 

  374. Duffy MJ, Crown J. Companion biomarkers: paving the pathway to personalized treatment for cancer. Clin Chem. 2013;59(10):1447–56. PM:23656699.

    CAS  PubMed  Google Scholar 

  375. FDA. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). U S Food and Drug Administration. 2014. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm.

  376. Werner HM, Mills GB, Ram PT. Cancer Systems Biology: a peek into the future of patient care? Nat Rev Clin Oncol. 2014;11(3):167–76. PM:24492837.

    PubMed Central  PubMed  Google Scholar 

  377. Bulusu KC, Tym JE, Coker EA. Schierz AC. Al-Lazikani B canSAR: updated cancer research and drug discovery knowledgebase Nucleic Acids Res. 2014;42(Database issue):D1040–7. PM:24304894.

    CAS  PubMed  Google Scholar 

  378. Cline MS, Craft B, Swatloski T, Goldman M, Ma S, Haussler D, et al. Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser. Sci Rep. 2013;3:2652. PM:24084870.

    PubMed Central  PubMed  Google Scholar 

  379. Goldman M, Craft B, Swatloski T, Ellrott K, Cline M, Diekhans M, et al. The UCSC Cancer Genomics Browser: update 2013. Nucleic Acids Res. 2013;41(Database issue):D949–54. PM:23109555.

    PubMed Central  CAS  PubMed  Google Scholar 

  380. Goldman M, Craft B, Swatloski T, Cline M, Morozova O, Diekhans M, et al. The UCSC cancer genomics browser: update 2015. Nucleic Acids Res. 2014;11. PM:25392408.

    Google Scholar 

  381. Boja ES, Rodriguez H. Proteogenomic convergence for understanding cancer pathways and networks. Clin Proteomics. 2014;11(1):22. PM:24994965.

    PubMed Central  PubMed  Google Scholar 

  382. Schroeder MP, Gonzalez-Perez A, Lopez-Bigas N. Visualizing multidimensional cancer genomics data. Genome Med. 2013;5(1):9. PM:23363777.

    PubMed Central  PubMed  Google Scholar 

  383. Mills GB. An emerging toolkit for targeted cancer therapies. Genome Res. 2012;22(2):177–82. PM:22301131.

    PubMed Central  CAS  PubMed  Google Scholar 

  384. Welch JS, Westervelt P, Ding L, Larson DE, Klco JM, Kulkarni S, et al. Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA. 2011;305(15):1577–84. PM:21505136.

    PubMed Central  CAS  PubMed  Google Scholar 

  385. Aksoy BA, Demir E, Babur O, Wang W, Jing X, Schultz N, et al. Prediction of individualized therapeutic vulnerabilities in cancer from genomic profiles. Bioinformatics. 2014;30(14):2051–9. PM:24665131.

    PubMed Central  CAS  PubMed  Google Scholar 

  386. Van Allen EM, Wagle N, Stojanov P, Perrin DL, Cibulskis K, Marlow S, et al. Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine. Nat Med. 2014;20(6):682–8. PM:24836576.

    PubMed Central  PubMed  Google Scholar 

  387. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50. PM:16199517.

    PubMed Central  CAS  PubMed  Google Scholar 

  388. Efroni S, Schaefer CF, Buetow KH. Identification of key processes underlying cancer phenotypes using biologic pathway analysis. PLoS One. 2007;2(5), e425. PM:17487280.

    PubMed Central  PubMed  Google Scholar 

  389. Eifert C, Powers RS. From cancer genomes to oncogenic drivers, tumour dependencies and therapeutic targets. Nat Rev Cancer. 2012;12(8):572–8. PM:22739505.

    CAS  PubMed  Google Scholar 

  390. Sedgewick AJ, Benz SC, Rabizadeh S, Soon-Shiong P, Vaske CJ. Learning subgroup-specific regulatory interactions and regulator independence with PARADIGM. Bioinformatics. 2013;29(13):i62–70. PM:23813010.

    PubMed Central  CAS  PubMed  Google Scholar 

  391. Vaske CJ, Benz SC, Sanborn JZ, Earl D, Szeto C, Zhu J, et al. Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM. Bioinformatics. 2010;26(12):i237–45. PM:20529912.

    PubMed Central  CAS  PubMed  Google Scholar 

  392. Greenblum SI, Efroni S, Schaefer CF, Buetow KH. The PathOlogist: an automated tool for pathway-centric analysis. BMC Bioinformatics. 2011;12:133. PM:21542931.

    PubMed Central  PubMed  Google Scholar 

  393. Kramer F, Bayerlova M, Beissbarth T. R-based software for the integration of pathway data into bioinformatic algorithms. Biology (Basel). 2014;3(1):85–100. PM:24833336.

    Google Scholar 

  394. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2011;27(3):431–2. PM:21149340.

    PubMed Central  CAS  PubMed  Google Scholar 

  395. Saito R, Smoot ME, Ono K, Ruscheinski J, Wang PL, Lotia S, et al. A travel guide to cytoscape plugins. Nat Methods. 2012;9(11):1069–76. PM:23132118.

    PubMed Central  CAS  PubMed  Google Scholar 

  396. Su G, Morris JH, Demchak B, Bader GD. Biological network exploration with cytoscape 3. Curr Protoc Bioinformatics. 2014;47:8. PM:25199793.

    PubMed  Google Scholar 

  397. Lotia S, Montojo J, Dong Y, Bader GD, Pico AR. Cytoscape app store. Bioinformatics. 2013;29(10):1350–1. PM:23595664.

    PubMed Central  CAS  PubMed  Google Scholar 

  398. Smink LJ, Helton EM, Healy BC, Cavnor CC, Lam AC, Flamez D, et al. T1DBase, a community web-based resource for type 1 diabetes research. Nucleic Acids Res. 2005;33(Database issue):D544–9. PM:15608258.

    PubMed Central  CAS  PubMed  Google Scholar 

  399. Alcaraz N, Friedrich T, Kotzing T, Krohmer A, Muller J, Pauling J, et al. Efficient key pathway mining: combining networks and OMICS data. Integr Biol (Camb). 2012;4(7):756–64. PM:22353882.

    Google Scholar 

  400. Leng D, Huan C, Xie T, Liang J, Wang J, Dai H, et al. Meta-analysis of genetic programs between idiopathic pulmonary fibrosis and sarcoidosis. PLoS One. 2013;8(8), e71059. PM:23967151.

    PubMed Central  CAS  PubMed  Google Scholar 

  401. Zhang ZG, Cao H, Liu G, Fan HM, Liu ZM. Bioinformatic analysis of microarray data reveals several key genes related to heart failure. Eur Rev Med Pharmacol Sci. 2013;17(18):2441–8. PM:24089221.

    PubMed  Google Scholar 

  402. Gupta A, Mohanty P, Bhatnagar S. Integrative analysis of ocular complications in atherosclerosis unveils pathway convergence and crosstalk. J Recept Signal Transduct Res. 2014;1–16. PM:25055025.

    Google Scholar 

  403. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, et al. Integration of biological networks and gene expression data using Cytoscape. Nat Protoc. 2007;2(10):2366–82. PM:17947979.

    PubMed Central  CAS  PubMed  Google Scholar 

  404. Wallace IM, Bader GD, Giaever G, Nislow C. Displaying chemical information on a biological network using Cytoscape. Methods Mol Biol. 2011;781:363–76. PM:21877291.

    CAS  PubMed  Google Scholar 

  405. Bauer-Mehren A. Integration of genomic information with biological networks using Cytoscape. Methods Mol Biol. 2013;1021:37–61. PM:23715979.

    PubMed  Google Scholar 

  406. Liu H, Beck TN, Golemis EA, Serebriiskii IG. Integrating in silico resources to map a signaling network. Methods Mol Biol. 2014;1101:197–245. PM:24233784.

    CAS  PubMed  Google Scholar 

  407. Broad Institute. Broad integrative genomics portal. Broad Institute. 2014. http://www.broadinstitute.org/scientific-community/software?page=3.

  408. Galaxy Team. Galaxy: an open platform for supporting computational research in the life sciences: public galaxy service. Galaxy. 2014. http://usegalaxy.org.

  409. Blankenberg D, Taylor J, Schenck I, He J, Zhang Y, Ghent M, et al. A framework for collaborative analysis of ENCODE data: making large-scale analyses biologist-friendly. Genome Res. 2007;17(6):960–4. PM:17568012.

    PubMed Central  CAS  PubMed  Google Scholar 

  410. Taylor J, Schenck I, Blankenberg D, Nekrutenko A. Using galaxy to perform large-scale interactive data analyses. Curr Protoc Bioinformatics. 2007;Chapter 10:Unit, PM:18428782.

    Google Scholar 

  411. Goecks J, Nekrutenko A, Taylor J. Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol. 2010;11(8):R86. PM:20738864.

    PubMed Central  PubMed  Google Scholar 

  412. Pennisi E. Genomics. Inching toward the 3D genome. Science. 2015;347(6217):10. PM:25554765.

    Google Scholar 

  413. Graur D, Zheng Y, Price N, Azevedo RB, Zufall RA, Elhaik E. On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol Evol. 2013;5(3):578–90. PM:23431001.

    PubMed Central  PubMed  Google Scholar 

  414. Eddy SR. The C-value paradox, junk DNA and ENCODE. Curr Biol. 2012;22(21):R898–9. PM:23137679.

    CAS  PubMed  Google Scholar 

  415. Doolittle WF. Is junk DNA bunk? A critique of ENCODE. Proc Natl Acad Sci U S A. 2013;110(14):5294–300. PM:23479647.

    PubMed Central  CAS  PubMed  Google Scholar 

  416. Watson J. Oxidants, antioxidants and the current incurability of metastatic cancers. Open Biol. 2013;3(1):120144. PM:23303309.

    PubMed Central  PubMed  Google Scholar 

  417. Boghog2. Signal transduction pathways image; in [Public Domain] via Wikimedia Commons. Wikimedia Commons. 2014. http://commons.wikimedia.org/wiki/File:Signal_transduction_pathways.png#mediaviewer/File:Signal_transduction_pathways.png.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carleton T. Garrett M.D., Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Garrett, C.T. (2015). Molecular Biology Basics in the “Omics” Era: Genes to Proteins. In: Idowu, M., Dumur, C., Garrett, C. (eds) Molecular Oncology Testing for Solid Tumors. Springer, Cham. https://doi.org/10.1007/978-3-319-16304-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-16304-8_1

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-16303-1

  • Online ISBN: 978-3-319-16304-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics