UBF an Essential Player in Maintenance of Active NORs and Nucleolar Formation

Chapter
First Online:
Part of the Protein Reviews book series (PRON, volume 15)

Abstract

Nucleolar organizer regions (NORs) are comprised of tandem arrays of ribosomal gene repeats. During interphase, ribosomal genes are transcribed by RNA polymerase I resulting in the formation of a nucleolus. Within nucleoli, an intricate and highly coordinated assembly pathway is responsible for the production of biology’s most complex machine, the ribosome. Upstream binding factor (UBF) binds extensively and plays a key role in organizing ribosomal gene chromatin throughout the cell cycle. It is responsible for the appearance of active NORs as secondary constrictions on metaphase chromosomes and its levels determine the proportion of ribosomal gene repeats that are active in a given cell type. Extensive UBF binding to NORs directs recruitment of many factors required in the early steps of ribosome biogenesis, thus enabling efficient nucleolar reformation. Finally, we reveal that UBF, once thought to be restricted to vertebrates, is present in many animal phyla.

Keywords

Ribosome Biogenesis Transcription Machinery Secondary Constriction rDNA Repeat rDNA Transcription 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

We would like to thank Tom Moss and Olivier Gadal for communicating results prior to publication. Work in the McStay laboratory is funded by PI grant number 07/IN.1/B924 from Science Foundation Ireland. Alice Grob is funded by a postdoctoral fellowship from IRCSET.

References

  1. Alzuherri HM, White RJ (1999) Regulation of RNA polymerase I transcription in response to F9 embryonal carcinoma stem cell differentiation. J Biol Chem 274:4328–4334PubMedCrossRefGoogle Scholar
  2. Beckmann H, Chen JL, O’Brien T, Tjian R (1995) Coactivator and promoter-selective properties of RNA polymerase I TAFs. Science 270:1506–1509PubMedCrossRefGoogle Scholar
  3. Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M, Kouzarides T (2010) Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 143:470–484PubMedCrossRefGoogle Scholar
  4. Bazett-Jones DP, Leblanc B, Herfort M, Moss T (1994) Short-range DNA looping by the Xenopus HMG-box transcription factor, xUBF. Science 264:1134–1137PubMedCrossRefGoogle Scholar
  5. Birnstiel ML, Wallace H, Sirlin JL, Fischberg M (1966) Localization of the ribosomal DNA complements in the nucleolar organizer region of Xenopus laevis. Natl Cancer Inst Monogr 23:431–447PubMedGoogle Scholar
  6. Brandenburger Y, Arthur JF, Woodcock EA, Du XJ, Gao XM, Autelitano DJ, Rothblum LI, Hannan RD (2003) Cardiac hypertrophy in vivo is associated with increased expression of the ribosomal gene transcription factor UBF. FEBS Lett 548:79–84PubMedCrossRefGoogle Scholar
  7. Brown DD, Gurdon JB (1964) Absence of ribosomal RNA synthesis in the anucleolate mutant of Xenopus laevis. Proc Natl Acad Sci USA 51:139–146PubMedCrossRefGoogle Scholar
  8. Caburet S, Conti C, Schurra C, Lebofsky R, Edelstein SJ, Bensimon A (2005) Human ribosomal RNA gene arrays display a broad range of palindromic structures. Genome Res 15: 1079–1085PubMedCrossRefGoogle Scholar
  9. Chen HK, Pai CY, Huang JY, Yeh NH (1999) Human Nopp 140, which interacts with RNA polymerase I: implications for rRNA gene transcription and nucleolar structural organization. Mol Cell Biol 19:8536–8546PubMedGoogle Scholar
  10. Conconi A, Widmer RM, Koller T, Sogo JM (1989) Two different chromatin structures coexist in ribosomal RNA genes throughout the cell cycle. Cell 57:753–761PubMedCrossRefGoogle Scholar
  11. Copenhaver GP, Putnam CD, Denton ML, Pikaard CS (1994) The RNA polymerase I transcription factor UBF is a sequence-tolerant HMG-box protein that can recognize structured nucleic acids. Nucleic Acids Res 22:2651–2657PubMedCrossRefGoogle Scholar
  12. Datta PK, Budhiraja S, Reichel RR, Jacob ST (1997) Regulation of ribosomal RNA gene transcription during retinoic acid-induced differentiation of mouse teratocarcinoma cells. Exp Cell Res 231:198–205PubMedCrossRefGoogle Scholar
  13. Dev VG, Tantravahi R, Miller DA, Miller OJ (1977) Nucleolus organizers in Mus musculus subspecies and in the RAG mouse cell line. Genetics 86:389–398PubMedGoogle Scholar
  14. Dragon F, Gallagher JE, Compagnone-Post PA, Mitchell BM, Porwancher KA, Wehner KA, Wormsley S, Settlage RE, Shabanowitz J, Osheim Y et al (2002) A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis. Nature 417:967–970PubMedCrossRefGoogle Scholar
  15. Drakas R, Tu X, Baserga R (2004) Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase. Proc Natl Acad Sci USA 101:9272–9276PubMedCrossRefGoogle Scholar
  16. Dundr M, Hoffmann-Rohrer U, Hu Q, Grummt I, Rothblum LI, Phair RD, Misteli T (2002) A kinetic framework for a mammalian RNA polymerase in vivo. Science 298:1623–1626PubMedCrossRefGoogle Scholar
  17. Edstrom JE, Grampp W, Schor N (1961) The intracellular distribution and heterogeneity of ribonucleic acid in starfish oocytes. J Biophys Biochem Cytol 11:549–557PubMedCrossRefGoogle Scholar
  18. Gadal O, Labarre S, Boschiero C, Thuriaux P (2002) Hmo1, an HMG-box protein, belongs to the yeast ribosomal DNA transcription system. EMBO J 21:5498–5507PubMedCrossRefGoogle Scholar
  19. Gallagher JE, Dunbar DA, Granneman S, Mitchell BM, Osheim Y, Beyer AL, Baserga SJ (2004) RNA polymerase I transcription and pre-rRNA processing are linked by specific SSU processome components. Genes Dev 18:2506–2517PubMedCrossRefGoogle Scholar
  20. Goessens G (1984) Nucleolar structure. Int Rev Cytol 87:107–158PubMedCrossRefGoogle Scholar
  21. Gonzalez IL, Sylvester JE (1995) Complete sequence of the 43-kb human ribosomal DNA repeat: analysis of the intergenic spacer. Genomics 27:320–328PubMedCrossRefGoogle Scholar
  22. Goodpasture C, Bloom SE (1975) Visualization of nucleolar organizer regions in mammalian chromosomes using silver staining. Chromosoma 53:37–50PubMedCrossRefGoogle Scholar
  23. Grandi P, Rybin V, Bassler J, Petfalski E, Strauss D, Marzioch M, Schafer T, Kuster B, Tschochner H, Tollervey D et al (2002) 90S Pre-ribosomes include the 35S pre-rRNA, the U3 snoRNP, and 40S subunit processing factors but predominantly lack 60S synthesis factors. Mol Cell 10:105–115PubMedCrossRefGoogle Scholar
  24. Granneman S, Baserga SJ (2004) Ribosome biogenesis: of knobs and RNA processing. Exp Cell Res 296:43–50PubMedCrossRefGoogle Scholar
  25. Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D, Sirri V (2009) Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis. J Cell Sci 122:489–498PubMedCrossRefGoogle Scholar
  26. Grozdanov P, Georgiev O, Karagyozov L (2003) Complete sequence of the 45-kb mouse ribosomal DNA repeat: analysis of the intergenic spacer. Genomics 82:637–643PubMedCrossRefGoogle Scholar
  27. Grummt I (2003) Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17:1691–1702PubMedCrossRefGoogle Scholar
  28. Grummt I, Pikaard CS (2003) Epigenetic silencing of RNA polymerase I transcription. Nat Rev Mol Cell Biol 4:641–649PubMedCrossRefGoogle Scholar
  29. Grummt I, Maier U, Ohrlein A, Hassouna N, Bachellerie JP (1985) Transcription of mouse rDNA terminates downstream of the 3′ end of 28S RNA and involves interaction of factors with repeated sequences in the 3′ spacer. Cell 43:801–810PubMedCrossRefGoogle Scholar
  30. Grummt I, Kuhn A, Bartsch I, Rosenbauer H (1986) A transcription terminator located upstream of the mouse rDNA initiation site affects rRNA synthesis. Cell 47:901–911PubMedCrossRefGoogle Scholar
  31. Hall DB, Wade JT, Struhl K (2006) An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae. Mol Cell Biol 26:3672–3679PubMedCrossRefGoogle Scholar
  32. Haltiner MM, Smale ST, Tjian R (1986) Two distinct promoter elements in the human rRNA gene identified by linker scanning mutagenesis. Mol Cell Biol 6:227–235PubMedGoogle Scholar
  33. Hanada K, Song CZ, Yamamoto K, Yano K, Maeda Y, Yamaguchi K, Muramatsu M (1996) RNA polymerase I associated factor 53 binds to the nucleolar transcription factor UBF and functions in specific rDNA transcription. Embo J 15:2217–2226PubMedCrossRefGoogle Scholar
  34. Hannan KM, Brandenburger Y, Jenkins A, Sharkey K, Cavanaugh A, Rothblum L, Moss T, Poortinga G, McArthur GA, Pearson RB et al (2003) mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol Cell Biol 23: 8862–8877PubMedCrossRefGoogle Scholar
  35. Hayano T, Yanagida M, Yamauchi Y, Shinkawa T, Isobe T, Takahashi N (2003) Proteomic analysis of human Nop56p-associated pre-ribosomal ribonucleoprotein complexes. Possible link between Nop56p and the nucleolar protein treacle responsible for Treacher Collins syndrome. J Biol Chem 278:34309–34319PubMedCrossRefGoogle Scholar
  36. Heitz E (1931) Die ursache der gesetzmassigen zahl, lage, form und grosse pflanzlicher nukleolen. Planta 12:775–844CrossRefGoogle Scholar
  37. Heliot L, Kaplan H, Lucas L, Klein C, Beorchia A, Doco-Fenzy M, Menager M, Thiry M, O’Donohue MF, Ploton D (1997) Electron tomography of metaphase nucleolar organizer regions: evidence for a twisted-loop organization. Mol Biol Cell 8:2199–2216PubMedGoogle Scholar
  38. Heliot L, Mongelard F, Klein C, O’Donohue MF, Chassery JM, Robert-Nicoud M, Usson Y (2000) Nonrandom distribution of metaphase AgNOR staining patterns on human acrocentric chromosomes. J Histochem Cytochem 48:13–20PubMedGoogle Scholar
  39. Henderson S, Sollner Webb B (1986) A transcriptional terminator is a novel element of the promoter of the mouse ribosomal RNA gene. Cell 47:891–900PubMedCrossRefGoogle Scholar
  40. Henderson AS, Warburton D, Atwood KC (1972) Location of ribosomal DNA in the human chromosome complement. Proc Natl Acad Sci USA 69:3394–3398PubMedCrossRefGoogle Scholar
  41. Hu CH, McStay B, Jeong SW, Reeder RH (1994) xUBF, an RNA polymerase I transcription factor, binds crossover DNA with low sequence specificity. Mol Cell Biol 14:2871–2882PubMedGoogle Scholar
  42. Jantzen HM, Admon A, Bell SP, Tjian R (1990) Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Nature 344:830–836PubMedCrossRefGoogle Scholar
  43. Jantzen HM, Chow AM, King DS, Tjian R (1992) Multiple domains of the RNA polymerase I activator hUBF interact with the TATA-binding protein complex hSL1 to mediate transcription. Genes Dev 6:1950–1963PubMedCrossRefGoogle Scholar
  44. Jordan P, Mannervik M, Tora L, Carmo-Fonseca M (1996) In vivo evidence that TATA-binding protein/SL1 colocalizes with UBF and RNA polymerase I when rRNA synthesis is either active or inactive. J Cell Biol 133:225–234PubMedCrossRefGoogle Scholar
  45. Junera HR, Masson C, Geraud G, Suja J, Hernandez-Verdun D (1997) Involvement of in situ conformation of ribosomal genes and selective distribution of upstream binding factor in rRNA transcription. Mol Biol Cell 8:145–156PubMedGoogle Scholar
  46. Kermekchiev M, Workman JL, Pikaard CS (1997) Nucleosome binding by the polymerase I transactivator upstream binding factor displaces linker histone H1. Mol Cell Biol 17:5833–5842PubMedGoogle Scholar
  47. Kortschak RD, Samuel G, Saint R, Miller DJ (2003) EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates. Curr Biol 13:2190–2195PubMedCrossRefGoogle Scholar
  48. Krogan NJ, Peng WT, Cagney G, Robinson MD, Haw R, Zhong G, Guo X, Zhang X, Canadien V, Richards DP et al (2004) High-definition macromolecular composition of yeast RNA-processing complexes. Mol Cell 13:225–239PubMedCrossRefGoogle Scholar
  49. Kuhn A, Grummt I (1987) A novel promoter in the mouse rDNA spacer is active in vivo and in vitro. EMBO J 6:3487–3492PubMedGoogle Scholar
  50. Kwon H, Green MR (1994) The RNA polymerase I transcription factor, upstream binding factor, interacts directly with the TATA box-binding protein. J Biol Chem 269:30140–30146PubMedCrossRefGoogle Scholar
  51. Labhart P, Reeder RH (1984) Enhancer-like properties of the 60/81 bp elements in the ribosomal gene spacer of Xenopus laevis. Cell 37:285–289PubMedCrossRefGoogle Scholar
  52. Langst G, Blank TA, Becker PB, Grummt I (1997) RNA polymerase I transcription on nucleosomal templates: the transcription termination factor TTF-I induces chromatin remodeling and relieves transcriptional repression. EMBO J 16:760–768PubMedCrossRefGoogle Scholar
  53. Larson DE, Xie W, Glibetic M, O’Mahony D, Sells BH, Rothblum LI (1993) Coordinated decreases in rRNA gene transcription factors and rRNA synthesis during muscle cell differentiation. Proc Natl Acad Sci USA 90:7933–7936PubMedCrossRefGoogle Scholar
  54. Learned RM, Learned TK, Haltiner MM, Tjian RT (1986) Human rRNA transcription is modulated by the coordinate binding of two factors to an upstream control element. Cell 45:847–857PubMedCrossRefGoogle Scholar
  55. Leung AK, Gerlich D, Miller G, Lyon C, Lam YW, Lleres D, Daigle N, Zomerdijk J, Ellenberg J, Lamond AI (2004) Quantitative kinetic analysis of nucleolar breakdown and reassembly during mitosis in live human cells. J Cell Biol 166:787–800PubMedCrossRefGoogle Scholar
  56. Li J, Langst G, Grummt I (2006) NoRC-dependent nucleosome positioning silences rRNA genes. EMBO J 25:5735–5741PubMedCrossRefGoogle Scholar
  57. Liu M, Tu X, Ferrari-Amorotti G, Calabretta B, Baserga R (2007) Downregulation of the upstream binding factor1 by glycogen synthase kinase3beta in myeloid cells induced to differentiate. J Cell Biochem 100:1154–1169PubMedCrossRefGoogle Scholar
  58. Mais C, Wright JE, Prieto JL, Raggett SL, McStay B (2005) UBF-binding site arrays form pseudo-NORs and sequester the RNA polymerase I transcription machinery. Genes Dev 19:50–64PubMedCrossRefGoogle Scholar
  59. McClintock B (1934) The relationship of a particular chromosomal element to the development of the nucleoli in Zea mays. Zeit Zellforsch Mik Anat 21:294–328CrossRefGoogle Scholar
  60. McStay B, Grummt I (2008) The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol 24:131–157PubMedCrossRefGoogle Scholar
  61. McStay B, Frazier MW, Reeder RH (1991) xUBF contains a novel dimerization domain essential for RNA polymerase I transcription. Genes Dev 5:1957–1968PubMedCrossRefGoogle Scholar
  62. McStay B, Sullivan GJ, Cairns C (1997) The Xenopus RNA polymerase I transcription factor, UBF, has a role in transcriptional enhancement distinct from that at the promoter. EMBO J 16:396–405PubMedCrossRefGoogle Scholar
  63. Meier UT, Blobel G (1994) NAP57, a mammalian nucleolar protein with a putative homolog in yeast and bacteria. J Cell Biol 127:1505–1514PubMedCrossRefGoogle Scholar
  64. Meraner J, Lechner M, Loidl A, Goralik-Schramel M, Voit R, Grummt I, Loidl P (2006) Acetylation of UBF changes during the cell cycle and regulates the interaction of UBF with RNA polymerase I. Nucleic Acids Res 34:1798–1806PubMedCrossRefGoogle Scholar
  65. Merz K, Hondele M, Goetze H, Gmelch K, Stoeckl U, Griesenbeck J (2008) Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules. Genes Dev 22:1190–1204PubMedCrossRefGoogle Scholar
  66. Miller OL Jr, Bakken AH (1972) Morphological studies of transcription. Acta Endocrinol Suppl (Copenh) 168:155–177Google Scholar
  67. Moss T, Birnstiel ML (1979) The putative promoter of a Xenopus laevis ribosomal gene is reduplicated. Nucleic Acids Res 6:3733–3743PubMedCrossRefGoogle Scholar
  68. Moss T, Langlois F, Gagnon-Kugler T, Stefanovsky V (2007) A housekeeper with power of attorney: the rRNA genes in ribosome biogenesis. Cell Mol Life Sci 64:29–49PubMedCrossRefGoogle Scholar
  69. Muramatsu M, Smetana K, Busch H (1963) Quantitative aspects of isolation of nucleoli of the Walker carcinosarcoma and liver of the rat. Cancer Res 23:510–522Google Scholar
  70. Newport J, Kirschner M (1982a) A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage. Cell 30:675–686PubMedCrossRefGoogle Scholar
  71. Newport J, Kirschner M (1982b) A major developmental transition in early Xenopus embryos: II. Control of the onset of transcription. Cell 30:687–696PubMedCrossRefGoogle Scholar
  72. O’Mahony DJ, Rothblum LI (1991) Identification of two forms of the RNA polymerase I transcription factor UBF. Proc Natl Acad Sci USA 88:3180–3184PubMedCrossRefGoogle Scholar
  73. O’Sullivan AC, Sullivan GJ, McStay B (2002) UBF binding in vivo is not restricted to regulatory sequences within the vertebrate ribosomal DNA repeat. Mol Cell Biol 22:657–668PubMedCrossRefGoogle Scholar
  74. Panov KI, Panova TB, Gadal O, Nishiyama K, Saito T, Russell J, Zomerdijk JC (2006) RNA ­polymerase I-specific subunit CAST/hPAF49 has a role in the activation of transcription by upstream binding factor. Mol Cell Biol 26:5436–5448PubMedCrossRefGoogle Scholar
  75. Perry RP, Errera M (1961) The role of the nucleolus in ribonucleic acid-and protein synthesis. I. Incorporation of cytidine into normal and nucleolar inactivated HeLa cells. Biochim Biophys Acta 49:47–57PubMedCrossRefGoogle Scholar
  76. Pikaard CS, McStay B, Schultz MC, Bell SP, Reeder RH (1989) The Xenopus ribosomal gene enhancers bind an essential polymerase I transcription factor, xUBF. Genes Dev 3:1779–1788PubMedCrossRefGoogle Scholar
  77. Pikaard CS, Pape LK, Henderson SL, Ryan K, Paalman MH, Lopata MA, Reeder RH, Sollner WB (1990) Enhancers for RNA polymerase I in mouse ribosomal DNA. Mol Cell Biol 10:4816–4825PubMedGoogle Scholar
  78. Poortinga G, Hannan KM, Snelling H, Walkley CR, Jenkins A, Sharkey K, Wall M, Brandenburger Y, Palatsides M, Pearson RB et al (2004) MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J 23:3325–3335PubMedCrossRefGoogle Scholar
  79. Poortinga G, Wall M, Sanij E, Siwicki K, Ellul J, Brown D, Holloway TP, Hannan RD, McArthur GA (2011) c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I availability during granulocyte differentiation. Nucleic Acids Res 39:3267–3281PubMedCrossRefGoogle Scholar
  80. Prieto JL, McStay B (2007) Recruitment of factors linking transcription and processing of ­pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells. Genes Dev 21:2041–2054PubMedCrossRefGoogle Scholar
  81. Prieto JL, McStay B (2008) Pseudo-NORs: a novel model for studying nucleoli. Biochim Biophys Acta 1783:2116–2123PubMedCrossRefGoogle Scholar
  82. Putnam CD, Pikaard CS (1992) Cooperative binding of the Xenopus RNA polymerase I transcription factor xUBF to repetitive ribosomal gene enhancers. Mol Cell Biol 12:4970–4980PubMedGoogle Scholar
  83. Putnam CD, Copenhaver GP, Denton ML, Pikaard CS (1994) The RNA polymerase I transactivator upstream binding factor requires its dimerization domain and high-mobility-group (HMG) box 1 to bend, wrap, and positively supercoil enhancer DNA. Mol Cell Biol 14:6476–6488PubMedGoogle Scholar
  84. Puvion-Dutilleul F (1983) Morphology of transcription at cellular and molecular levels. Int Rev Cytol 84:57–101PubMedCrossRefGoogle Scholar
  85. Raska I, Shaw PJ, Cmarko D (2006) Structure and function of the nucleolus in the spotlight. Curr Opin Cell Biol 18:325–334PubMedCrossRefGoogle Scholar
  86. Reeder RH, Pikaard CS, McStay B (1995) UBF, an architectural element for RNA polymerase I promoters. In: Eckstein F, Lilley DMJ (eds) Nucleic acids and molecular biology. Springer, Berlin, pp 251–263Google Scholar
  87. Ritossa FM, Spiegelman S (1965) Localization of DNA complementary to ribosomal RNA in the nucleolus organizer region of Drosophila melanogaster. Proc Natl Acad Sci USA 53:737–745PubMedCrossRefGoogle Scholar
  88. Ritossa FM, Atwood KC, Lindsley DL, Spiegelman S (1966) On the chromosomal distribution of DNA complementary to ribosomal and soluble RNA. Natl Cancer Inst Monogr 23:449–472PubMedGoogle Scholar
  89. Roussel P, Andre C, Masson C, Geraud G, Hernandez VD (1993) Localization of the RNA polymerase I transcription factor hUBF during the cell cycle. J Cell Sci 104:327–337PubMedGoogle Scholar
  90. Roussel P, Andre C, Comai L, Hernandez-Verdun D (1996) The rDNA transcription machinery is assembled during mitosis in active NORs and absent in inactive NORs. J Cell Biol 133:235–246PubMedCrossRefGoogle Scholar
  91. Russell J, Zomerdijk JC (2005) RNA-polymerase-I-directed rDNA transcription, life and works. Trends Biochem Sci 30:87–96PubMedCrossRefGoogle Scholar
  92. Saitoh Y, Laemmli UK (1994) Metaphase chromosome structure: bands arise from a differential folding path of the highly AT-rich scaffold. Cell 76:609–622PubMedCrossRefGoogle Scholar
  93. Sakai K, Ohta T, Minoshima S, Kudoh J, Wang Y, de Jong PJ, Shimizu N (1995) Human ribosomal RNA gene cluster: identification of the proximal end containing a novel tandem repeat sequence. Genomics 26:521–526PubMedCrossRefGoogle Scholar
  94. Sanij E, Poortinga G, Sharkey K, Hung S, Holloway TP, Quin J, Robb E, Wong LH, Thomas WG, Stefanovsky V et al (2008) UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol 183:1259–1274PubMedCrossRefGoogle Scholar
  95. Scheer U, Benavente R (1990) Functional and dynamic aspects of the mammalian nucleolus. Bioessays 12:14–21PubMedCrossRefGoogle Scholar
  96. Scheer U, Rose KM (1984) Localization of RNA polymerase I in interphase cells and mitotic chromosomes by light and electron microscopic immunocytochemistry. Proc Natl Acad Sci USA 81:1431–1435PubMedCrossRefGoogle Scholar
  97. Schmickel RD (1973) Quantitation of human ribosomal DNA: hybridization of human DNA with ribosomal RNA for quantitation and fractionation. Pediatr Res 7:5–12PubMedCrossRefGoogle Scholar
  98. Schneider DA, Michel A, Sikes ML, Vu L, Dodd JA, Salgia S, Osheim YN, Beyer AL, Nomura M (2007) Transcription elongation by RNA polymerase I is linked to efficient rRNA processing and ribosome assembly. Mol Cell 26:217–229PubMedCrossRefGoogle Scholar
  99. Shaffer LG, Lupski JR (2000) Molecular mechanisms for constitutional chromosomal rearrangements in humans. Annu Rev Genet 34:297–329PubMedCrossRefGoogle Scholar
  100. Sirri V, Roussel P, Hernandez-Verdun D (1999) The mitotically phosphorylated form of the transcription termination factor TTF-1 is associated with the repressed rDNA transcription machinery. J Cell Sci 112:3259–3268PubMedGoogle Scholar
  101. Sirri V, Roussel P, Hernandez-Verdun D (2000) In vivo release of mitotic silencing of ribosomal gene transcription does not give rise to precursor ribosomal RNA processing. J Cell Biol 148:259–270PubMedCrossRefGoogle Scholar
  102. Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D (2008) Nucleolus: the fascinating nuclear body. Histochem Cell Biol 129:13–31PubMedCrossRefGoogle Scholar
  103. Srivastava M, Begovic E, Chapman J, Putnam NH, Hellsten U, Kawashima T, Kuo A, Mitros T, Salamov A, Carpenter ML et al (2008) The Trichoplax genome and the nature of placozoans. Nature 454:955–960PubMedCrossRefGoogle Scholar
  104. Stefanovsky V, Moss T (2006) Regulation of rRNA synthesis in human and mouse cells is not determined by changes in active gene count. Cell Cycle 5:735–739PubMedCrossRefGoogle Scholar
  105. Stefanovsky VY, Pelletier G, Bazett-Jones DP, Crane-Robinson C, Moss T (2001a) DNA looping in the RNA polymerase I enhancesome is the result of non-cooperative in-phase bending by two UBF molecules. Nucleic Acids Res 29:3241–3247PubMedCrossRefGoogle Scholar
  106. Stefanovsky VY, Pelletier G, Hannan R, Gagnon-Kugler T, Rothblum LI, Moss T (2001b) An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF. Mol Cell 8:1063–1073PubMedCrossRefGoogle Scholar
  107. Stefanovsky V, Langlois F, Gagnon-Kugler T, Rothblum LI, Moss T (2006a) Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol Cell 21:629–639PubMedCrossRefGoogle Scholar
  108. Stefanovsky VY, Langlois F, Bazett-Jones D, Pelletier G, Moss T (2006b) ERK modulates DNA bending and enhancesome structure by phosphorylating HMG1-boxes 1 and 2 of the RNA polymerase I transcription factor UBF. Biochemistry 45:3626–3634PubMedCrossRefGoogle Scholar
  109. Stros M (2010) HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta 1799:101–113PubMedGoogle Scholar
  110. Stults DM, Killen MW, Pierce HH, Pierce AJ (2008) Genomic architecture and inheritance of human ribosomal RNA gene clusters. Genome Res 18:13–18PubMedCrossRefGoogle Scholar
  111. Stults DM, Killen MW, Williamson EP, Hourigan JS, Vargas HD, Arnold SM, Moscow JA, Pierce AJ (2009) Human rRNA gene clusters are recombinational hotspots in cancer. Cancer Res 69: 9096–9104PubMedCrossRefGoogle Scholar
  112. Suja JA, Gebrane-Younes J, Geraud G, Hernandez-Verdun D (1997) Relative distribution of rDNA and proteins of the RNA polymerase I transcription machinery at chromosomal NORs. Chromosoma 105:459–469PubMedCrossRefGoogle Scholar
  113. Sullivan GJ, Bridger JM, Cuthbert AP, Newbold RF, Bickmore WA, McStay B (2001) Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli. EMBO J 20:2867–2874PubMedCrossRefGoogle Scholar
  114. Sylvester JE, Gonzales IL, Mougey EB (2004) Structure and organisation of vertebrate ribosomal DNA. In: Olson MO (ed) The nucleolus. Kluwer Academic/Plenum, New York, pp 58–72Google Scholar
  115. Therman E, Susman B, Denniston C (1989) The nonrandom participation of human acrocentric chromosomes in Robertsonian translocations. Ann Hum Genet 53:49–65PubMedCrossRefGoogle Scholar
  116. Travers AA (2003) Priming the nucleosome: a role for HMGB proteins? EMBO Rep 4:131–136PubMedCrossRefGoogle Scholar
  117. Treiber DK, Zhai X, Jantzen HM, Essigmann JM (1994) Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor). Proc Natl Acad Sci USA 91:5672–5676PubMedCrossRefGoogle Scholar
  118. Tuan JC, Zhai W, Comai L (1999) Recruitment of TATA-binding protein-TAFI complex SL1 to the human ribosomal DNA promoter is mediated by the carboxy-terminal activation domain of upstream binding factor (UBF) and is regulated by UBF phosphorylation. Mol Cell Biol 19:2872–2879PubMedGoogle Scholar
  119. Valdez BC, Henning D, So RB, Dixon J, Dixon MJ (2004) The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor. Proc Natl Acad Sci USA 101:10709–10714PubMedCrossRefGoogle Scholar
  120. van de Nobelen S, Rosa-Garrido M, Leers J, Heath H, Soochit W, Joosen L, Jonkers I, Demmers J, van der Reijden M, Torrano V, Grosveld F, Delgado MD, Renkawitz R, Galjart N, Sleutels F (2010) CTCF regulates the local epigenetic state of ribosomal DNA repeats. Epigenetics Chromatin 3:19PubMedCrossRefGoogle Scholar
  121. Voit R, Grummt I (2001) Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription. Proc Natl Acad Sci USA 98:13631–13636PubMedCrossRefGoogle Scholar
  122. Voit R, Schnapp A, Kuhn A, Rosenbauer H, Hirschmann P, Stunnenberg HG, Grummt I (1992) The nucleolar transcription factor mUBF is phosphorylated by casein kinase II in the C-terminal hyperacidic tail which is essential for transactivation. EMBO J 11:2211–2218PubMedGoogle Scholar
  123. Voit R, Hoffmann M, Grummt I (1999) Phosphorylation by G1-specific cdk-cyclin complexes activates the nucleolar transcription factor UBF. EMBO J 18:1891–1899PubMedCrossRefGoogle Scholar
  124. Warner JR, Kim HS (2010) The fast track is cotranscriptional. Mol Cell 37:745–746PubMedCrossRefGoogle Scholar
  125. Werner MH, Huth JR, Gronenborn AM, Clore GM (1995) Molecular basis of human 46X, Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex. Cell 81:705–714PubMedCrossRefGoogle Scholar
  126. Xu Y, Yang W, Wu J, Shi Y (2002) Solution structure of the first HMG box domain in human upstream binding factor. Biochemistry 41:5415–5420PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Centre for Chromosome Biology, School of Natural SciencesNational University of Ireland GalwayGalwayIreland

Personalised recommendations