The nucleolus is a nuclear compartment that plays an important role in ribosome biogenesis. Some structural features and epigenetic patterns are shared between nucleolar and non-nucleolar compartments. For example, the location of transcriptionally active mRNA on extended chromatin loop species is similar to that observed for transcriptionally active ribosomal DNA (rDNA) genes on so-called Christmas tree branches. Similarly, nucleolus organizer region-bearing chromosomes located a distance from the nucleolus extend chromatin fibers into the nucleolar compartment. Specific epigenetic events, such as histone acetylation and methylation and DNA methylation, also regulate transcription of both rRNA- and mRNA-encoding loci. Here, we review the epigenetic mechanisms and structural features that regulate transcription of ribosomal and mRNA genes. We focus on similarities in epigenetic and structural regulation of chromatin in nucleoli and the surrounding non-nucleolar region and discuss the role of proteins, such as heterochromatin protein 1, fibrillarin, nucleolin, and upstream binding factor, in rRNA synthesis and processing.

Institute of Biophysics Academy of Sciences of the Czech Republic v v i Královopolská 135 CZ 612 65 Brno Czech Republic

Zobrazit více v PubMed

Arabi A, Wu S, Ridderstråle K, Bierhoff H, Shiue C, Fatyol K, Fahlén S, et al. (2005) c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol 7:303–310 PubMed

Bártová E, Harničarová A, Krejčí J, Strašák L, Kozubek S (2008a) Single-cell c-myc gene expression in relationship to nuclear domains. Chromosome Res 16:325–343 PubMed

Bártová E, Kozubek S (2006) Nuclear architecture in the light of gene expression and cell differentiation studies. Biol Cell 98:323–336 PubMed

Bártová E, Krejčí J, Harničarová A, Galiová G, Kozubek S (2008b) Histone modifications and nuclear architecture: a review. J Histochem Cytochem 56:711–721 PubMed PMC

Bártová E, Krejčí J, Harničarová A, Kozubek S (2008c) Differentiation of human embryonic stem cells induces condensation of chromosome territories and formation of heterochromatin protein 1 foci. Differentiation 76:24–32 PubMed

Bernstein E, Allis CD (2005) RNA meets chromatin. Genes Dev 19:1635–1655 PubMed

Boisvert FM, van Koningsbruggen S, Navascués J, Lamond AI (2007) The multifunctional nucleolus. Nat Rev Mol Cell Biol 8:574–585 PubMed

Bond VC, Wold B (1993) Nucleolar localization of myc transcripts. Mol Cell Biol 13:3221–3230 PubMed PMC

Branco MR, Pombo A (2006) Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol 4:e138. PubMed PMC

Bridger JM, Herrmann H, Münkel C, Lichter P (1998) Identification of an interchromosomal compartment by polymerization of nuclear-targeted vimentin. J Cell Sci 111:1241–1253 PubMed

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 15:1079–1085 PubMed PMC

Chen D, Dundr M, Wang C, Leung A, Lamond A, Misteli T, Huang S (2005) Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins. J Cell Biol 168:41–54 PubMed PMC

Clemson CM, McNeil JA, Willard HF, Lawrence JB (1996) XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol 132:259–275 PubMed PMC

Cmarko D, Verschure PJ, Rothblum LI, Hernandez-Verdun D, Amalric F, van Driel R, Fakan S (2000) Ultrastructural analysis of nucleolar transcription in cells microinjected with 5-bromo-UTP. Histochem Cell Biol 113:181–187 PubMed

Cook PR (1999) The organization of replication and transcription. Science 284:1790–1795 PubMed

Cremer M, Zinner R, Stein S, Albiez H, Wagler B, Cremer C, Cremer T (2004) Three dimensional analysis of histone methylation patterns in normal and tumor cell nuclei. Eur J Histochem 48:15–28 PubMed

Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301 PubMed

Cremer T, Lichter P, Borden J, Ward DC, Manuelidis L (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes. Hum Genet 80:235–246 PubMed

Cvačková Z, Albring KF, Koberna K, Ligasová A, Huber O, Raška I, Staňek D (2008) Pontin is localized in nucleolar fibrillar centers. Chromosoma 117:487–497 PubMed PMC

Dev VG, Tantravahi R, Miller DA, Miller OJ (1977) Nucleolus organizers in Mus musculus subspecies and in the RAG mouse cell line. Genetics 86:389–398 PubMed PMC

Dialynas GK, Vitalini MW, Wallrath LL (2008) Linking heterochromatin protein 1 (HP1) to cancer progression. Mutat Res 647:13–20 PubMed PMC

Dimario PJ (2004) Cell and molecular biology of nucleolar assembly and disassembly. Int Rev Cytol 239:99–178 PubMed

Dundr M, Hoffmann-Rohrer U, Hu Q, Grummt I, Rothblum LI, Phair RD, Misteli T (2002a) A kinetic framework for a mammalian RNA polymerase in vivo. Science 298:1623–1626 PubMed

Dundr M, McNally JG, Cohen J, Misteli T (2002b) Quantitation of GFP-fusion proteins in single living cells. J Struct Biol 140:92–99 PubMed

Erard MS, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F (1988) A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. Eur J Biochem 175:525–530 PubMed

Espada J, Ballestar E, Santoro R, Fraga MF, Villar-Garea A, Németh A, Lopez-Serra L, et al. (2007) Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells. Nucleic Acids Res 35:2191–2198 PubMed PMC

Fodor BD, Kubicek S, Yonezawa M, O'Sullivan RJ, Sengupta R, Perez-Burgos L, Opravil S, et al. (2006) Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes Dev 20:1557–1562 PubMed PMC

Frescas D, Guardavaccaro D, Bassermann F, Koyama-Nasu R, Pagano M (2007) JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature 450:309–313 PubMed

Ginisty H, Sicard H, Roger B, Bouvet P (1999) Structure and functions of nucleolin. J Cell Sci 112:761–772 PubMed

Goetze S, Mateos-Langerak J, Gierman HJ, de Leeuw W, Giromus O, Indemans MH, Koster J, et al. (2007) The three-dimensional structure of human interphase chromosomes is related to the transcriptome map. Mol Cell Biol 27:4475–4487 PubMed PMC

Gonzalez IL, Sylvester JE (1997) Beyond ribosomal DNA: on towards the telomere. Chromosoma 105:431–437 PubMed

González-Melendi P, Wells B, Beven AF, Shaw PJ (2001) Single ribosomal transcription units are linear, compacted Christmas trees in plant nucleoli. Plant J 27:223–233 PubMed

Granboulan N, Granboulan P (1965) Ultrastructure cytochemistry of the nucleolus. II. Study of the sites of RNA synthesis in the nucleolus and the nucleus. Exp Cell Res 38:604–619 PubMed

Grummt I (2003) Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17:1691–1702 PubMed

Hannan KM, Hannan RD, Smith SD, Jefferson LS, Lun M, Rothblum LI (2000) Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1. Oncogene 19:4988–4999 PubMed

Harničarová A, Kozubek S, Pacherník J, Krejčí J, Bártová E (2006) Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells. Exp Cell Res 312:4019–4035 PubMed

Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL (1998) A role for histone deacetylase activity in HDAC1-mediated transcriptional repression. Proc Natl Acad Sci USA 95:3519–3524 PubMed PMC

Henderson AS, Warburton D, Atwood KC (1972) Location of ribosomal DNA in the human chromosome complement. Proc Natl Acad Sci USA 69:3394–3398 PubMed PMC

Kalmárová M, Smirnov E, Kováčik L, Popov A, Raška I (2008) Positioning of the NOR-bearing chromosomes in relation to nucleoli in daughter cells after mitosis. Physiol Res 57:421–425 PubMed PMC

Koberna K, Malínský J, Pliss A, Masata M, Vecerova J, Fialová M, Bednár J, et al. (2002) Ribosomal genes in focus: new transcripts label the dense fibrillar components and form clusters indicative of “Christmas trees” in situ. J Cell Biol 157:743–748 PubMed PMC

Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705 PubMed

Kovařík A, Koukalová B, Lim KY, Matyášek R, Lichtenstein CP, Leitch AR, Bezděk M (2000) Comparative analysis of DNA methylation in tobacco heterochromatic sequences. Chromosome Res 8:527–541 PubMed

Krejčí J, Harničarová A, Kůrová J, Uhlířová R, Kozubek S, Legartová S, Hájek R, et al. (2008) Nuclear organization of PML bodies in leukaemic and multiple myeloma cells. Leuk Res 32:1866–1877 PubMed

Krejčí J, Harničarová A, Streitová D, Hájek R, Pour L, Kozubek S, Bártová E (2009) Epigenetics of multiple myeloma after treatment with cytostatics and gamma radiation. Leuk Res 33:1490–1498 PubMed

Küpper K, Kölbl A, Biener D, Dittrich S, von Hase J, Thormeyer T, Fiegler H, et al. (2007) Radial chromatin positioning is shaped by local gene density, not by gene expression. Chromosoma 116:285–306 PubMed PMC

Kurz A, Lampel S, Nickolenko JE, Bradl J, Benner A, Zirbel RM, Cremer T, et al. (1996) Active and inactive genes localize preferentially in the periphery of chromosome territories. J Cell Biol 135:1195–1205 PubMed PMC

Lanctôt C, Cheutin T, Cremer M, Cavalli G, Cremer T (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 8:104–115 PubMed

Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, et al. (2003) SUV39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol 13:1192–1200 PubMed

Leung AK, Gerlich D, Miller G, Lyon C, Lam YW, Lleres D, Daigle N, et al. (2004) Quantitative kinetic analysis of nucleolar breakdown and reassembly during mitosis in live human cells. J Cell Biol 166:787–800 PubMed PMC

Levsky JM, Shenoy SM, Pezo RC, Singer RH (2002) Single-cell gene expression profiling. Science 297:836–840 PubMed

Louvet E, Junéra HR, Le Panse S, Hernandez-Verdun D (2005) Dynamics and compartmentation of the nucleolar processing machinery. Exp Cell Res 304:457–470 PubMed

Maggi LB Jr, Weber JD (2005) Nucleolar adaptation in human cancer. Cancer Invest 23:599–608 PubMed PMC

Mahy NL, Perry PE, Bickmore WA (2002) Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH. J Cell Biol 159:753–763 PubMed PMC

Maison C, Bailly D, Peters AH, Quivy JP, Roche D, Taddei A, Lachner M, et al. (2002) Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat Genet 30:329–334 PubMed

McKeown PC, Shaw PJ (2009) Chromatin: linking structure and function in the nucleolus. Chromosoma 118:11–23 PubMed

McStay B, Grummt I (2008) The epigenetics of rRNA genes: from molecular to chromosome biology. Annu Rev Cell Dev Biol 24:131–157 PubMed

Metzger E, Wissmann M, Yin N, Müller JM, Schneider R, Peters AH, Günther T, et al. (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437:436–439 PubMed

Miller OL Jr, Beatty BR (1969) Visualization of nucleolar genes. Science 164:955–957 PubMed

Miralles F, Visa N (2006) Actin in transcription and transcription regulation. Curr Opin Cell Biol 18:261–266 PubMed

Misteli T (2001) The concept of self-organization in cellular architecture. J Cell Biol 155:181–185 PubMed PMC

Mosgoeller W, Schöfer C, Steiner M, Sylvester JE, Hozák P (2001) Arrangement of ribosomal genes in nucleolar domains revealed by detection of “Christmas tree” components. Histochem Cell Biol 116:495–505 PubMed

Murray K (1964) The occurrence of epsilon-N-methyl lysine in histones. Biochemistry 3:10–15 PubMed

Neusser M, Schubel V, Koch A, Cremer T, Müller S (2007) Evolutionarily conserved, cell type and species-specific higher order chromatin arrangements in interphase nuclei of primates. Chromosoma 116:307–320 PubMed

Nicol SM, Causevic M, Prescott AR, Fuller-Pace FV (2000) The nuclear DEAD box RNA helicase p68 interacts with the nucleolar protein fibrillarin and colocalizes specifically in nascent nucleoli during telophase. Exp Cell Res 257:272–278 PubMed

Olson MO, Dundr M (2005) The moving parts of the nucleolus. Histochem Cell Biol 123:203–216 PubMed

Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, et al. (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36:1065–1071 PubMed

Parlato R, Kreiner G, Erdmann G, Rieker C, Stotz S, Savenkova E, Berger S, et al. (2008) Activation of an endogenous suicide response after perturbation of rRNA synthesis leads to neurodegeneration in mice. J Neurosci 28:12759–12764 PubMed PMC

Peng JC, Karpen GH (2007) H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability. Nat Cell Biol 9:25–35 PubMed PMC

Phair RD, Misteli T (2000) High mobility of proteins in the mammalian cell nucleus. Nature 404:604–609 PubMed

Philimonenko VV, Zhao J, Iben S, Dingová H, Kyselá K, Kahle M, Zentgraf H, et al. (2004) Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol 6:1165–1172 PubMed

Pikaard CS (1999) Nucleolar dominance and silencing of transcription. Trends Plant Sci 4:478–483 PubMed

Pinkel D, Landegent J, Collins C, Fuscoe J, Segraves R, Lucas J, Gray J (1988) Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci 85:9138–9142 PubMed PMC

Politz JC, Tuft RA, Pederson T (2003) Diffusion-based transport of nascent ribosomes in the nucleus. Mol Biol Cell 14:4805–4812 PubMed PMC

Poortinga G, Hannan KM, Snelling H, Walkley CR, Jenkins A, Sharkey K, Wall M, et al. (2004) MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J 23:3325–3335 PubMed PMC

Prieto JL, McStay B (2005) Nucleolar biogenesis: the first small steps. Biochem Soc Trans 33:1441–1443 PubMed

Raška I (2003) Oldies but goldies: searching for Christmas trees within the nucleolar architecture. Trends Cell Biol 13:517–525 PubMed

Raška I, Dundr M, Koberna K, Melčák I, Risueno MC, Török I (1995) Does the synthesis of ribosomal RNA take place within nucleolar fibrillar centers or dense fibrillar components? A critical appraisal. J Struct Biol 114:1–22 PubMed

Raška I, Koberna K, Malínský J, Fidlerová H, Mašata M (2004) The nucleolus and transcription of ribosomal genes. Biol Cell 96:579–594 PubMed

Raška I, Shaw PJ, Cmarko D (2006) New insights into nucleolar architecture and activity. Int Rev Cytol 255:177–235 PubMed

Rice JC, Allis CD (2001) Histone methylation versus histone acetylation: new insights into epigenetic regulation. Curr Opin Cell Biol 13:263–273 PubMed

Royo F, Paz N, Espinosa L, McQueen PG, Vellón L, Parada LA (2009) Spatial link between nucleoli and expression of the Zac1 gene. Chromosoma 118:711–722 PubMed PMC

Russell J, Zomerdijk JC (2005) RNA-polymerase-I-directed rDNA transcription, life and works. Trends Biochem Sci 30:87–96 PubMed PMC

Saccone S, Federico C, Bernardi G (2002) Localization of the gene-richest and the gene-poorest isochores in the interphase nuclei of mammals and birds. Gene 300:169–178 PubMed

Salminen A, Kaarniranta K (2009) SIRT1 regulates the ribosomal DNA locus: epigenetic candles twinkle longevity in the Christmas tree. Biochem Biophys Res Commun 378:6–9 PubMed

Santoro R, Grummt I (2005) Epigenetic mechanism of rRNA gene silencing: temporal order of NoRC-mediated histone modification, chromatin remodeling, and DNA methylation. Mol Cell Biol 25:2539–2546 PubMed PMC

Santoro R, Li J, Grummt I (2002) The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription. Nat Genet 32:393–396 PubMed

Scheer U, Benavente R (1990) Functional and dynamic aspects of the mammalian nucleolus. Bioessays 12:14–21 PubMed

Scheuermann MO, Tajbakhsh J, Kurz A, Saracoglu K, Eils R, Lichter P (2004) Topology of genes and nontranscribed sequences in human interphase nuclei. Exp Cell Res 301:266–279 PubMed

Schmitz KM, Schmitt N, Hoffmann-Rohrer U, Schäfer A, Grummt I, Mayer C (2009) TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol Cell 33:344–353 PubMed

Schübeler D, Groudine M, Bender MA (2001) The murine beta-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes. Proc Natl Acad Sci USA 98:11432–11437 PubMed PMC

Shav-Tal Y, Blechman J, Darzacq X, Montagna C, Dye BT, Patton JG, Singer RH, et al. (2005) Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition. Mol Biol Cell 16:2395–2413 PubMed PMC

Shaw PJ, Abranches R, Paula Santos A, Beven AF, Stoger E, Wegel E, González-Melendi P (2002) The architecture of interphase chromosomes and nucleolar transcription sites in plants. J Struct Biol 140:31–38 PubMed

Shaw PJ, Jordan EG (1995) The nucleolus. Annu Rev Cell Dev Biol 11:93–121 PubMed

Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, et al. (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953 PubMed

Shimizu N, Kawamoto JK, Utani K (2007) Regulation of c-myc through intranuclear localization of its RNA subspecies. Biochem Biophys Res Commun 359:806–810 PubMed

Skalníková M, Bártová E, Ulman V, Matula P, Svoboda D, Harnicarová A, Kozubek M, et al. (2007) Distinct patterns of histone methylation and acetylation in human interphase nuclei. Physiol Res 56:797–806 PubMed

Solovei I, Kreysing M, Lanctôt C, Kösem S, Peichl L, Cremer T, Guck J, et al. (2009) Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137:356–368 PubMed

Strašák L, Bártová E, Harničarová A, Galiová G, Krejčí J, Kozubek S (2009) H3K9 acetylation and radial chromatin positioning. J Cell Physiol 220:91–101 PubMed

Strohner R, Nemeth A, Jansa P, Hofmann-Rohrer U, Santoro R, Längst G, Grummt I (2001) NoRC: a novel member of mammalian ISWI-containing chromatin remodeling machines. EMBO J 20:4892–4900 PubMed PMC

Takizawa T, Gudla PR, Guo L, Lockett S, Misteli T (2008) Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. Genes Dev 22:489–498 PubMed PMC

Tanabe H, Müller S, Neusser M, von Hase J, Calcagno E, Cremer M, Solovei I, et al. (2002) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc Natl Acad Sci USA 99:4424–4429 PubMed PMC

Thiry M, Cheutin T, O'Donohue MF, Kaplan H, Ploton D (2000) Dynamics and three-dimensional localization of ribosomal RNA within the nucleolus. RNA 6:1750–1761 PubMed PMC

Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439:811–816 PubMed

Volpi EV, Chevret E, Jones T, Vatcheva R, Williamson J, Beck S, Campbell RD, et al. (2000) Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J Cell Sci 113:1565–1576 PubMed

Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, et al. (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125:467–481 PubMed

Wiblin AE, Cui W, Clark AJ, Bickmore WA (2005) Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells. J Cell Sci 118:3861–3868 PubMed

Williams RR, Broad S, Sheer D, Ragoussis J (2002) Subchromosomal positioning of the epidermal differentiation complex (EDC) in keratinocyte and lymphoblast interphase nuclei. Exp Cell Res 272:163–175 PubMed

Worton RG, Sutherland J, Sylvester JE, Willard HF, Bodrug S, Dubé I, Duff C, et al. (1988) Human ribosomal RNA genes: orientation of the tandem array and conservation of the 5′ end. Science 239:64–68 PubMed

Yan Q, Cho E, Lockett S, Muegge K (2003) Association of Lsh, a regulator of DNA methylation, with pericentromeric heterochromatin is dependent on intact heterochromatin. Mol Cell Biol 23:8416–8428 PubMed PMC

Yuan X, Feng W, Imhof A, Grummt I, Zhou Y (2007) Activation of RNA polymerase I transcription by cockayne syndrome group B protein and histone methyltransferase G9a. Mol Cell 27:585–595 PubMed

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

Zhang Y, Reinberg D (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev 15:2343–2360 PubMed

Zhou Y, Grummt I (2005) The PHD finger/bromodomain of NoRC interacts with acetylated histone H4K16 and is sufficient for rDNA silencing. Curr Biol 15:1434–1438 PubMed

Zhou Y, Santoro R, Grummt I (2002) The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J 21:4632–4640 PubMed PMC

Zink D, Amaral MD, Englmann A, Lang S, Clarke LA, Rudolph C, Alt F, et al. (2004) Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei. J Cell Biol 166:815–825 PubMed PMC

Zinner R, Albiez H, Walter J, Peters AH, Cremer T, Cremer M (2006) Histone lysine methylation patterns in human cell types are arranged in distinct three-dimensional nuclear zones. Histochem Cell Biol 125:3–19 PubMed

Zirbel RM, Mathieu UR, Kurz A, Cremer T, Lichter P (1993) Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries. Chromosome Res 1:93–106 PubMed

Discontinuous transcription of ribosomal DNA in human cells

Fluctuations of pol I and fibrillarin contents of the nucleoli

Nucleolar Reorganization Upon Site-Specific Double-Strand Break Induction

Reproduction of the FC/DFC units in nucleoli