Chromosoma

, Volume 116, Issue 3, pp 285–306 | Cite as

Radial chromatin positioning is shaped by local gene density, not by gene expression

  • Katrin Küpper
  • Alexandra Kölbl
  • Dorothee Biener
  • Sandra Dittrich
  • Johann von Hase
  • Tobias Thormeyer
  • Heike Fiegler
  • Nigel P. Carter
  • Michael R. Speicher
  • Thomas Cremer
  • Marion Cremer
Research Article

Abstract

G- and R-bands of metaphase chromosomes are characterized by profound differences in gene density, CG content, replication timing, and chromatin compaction. The preferential localization of gene-dense, transcriptionally active, and early replicating chromatin in the nuclear interior and of gene-poor, later replicating chromatin at the nuclear envelope has been demonstrated to be evolutionary-conserved in various cell types. Yet, the impact of different local chromatin features on the radial nuclear arrangement of chromatin is still not well understood. In particular, it is not known whether radial chromatin positioning is preferentially shaped by local gene density per se or by other related parameters such as replication timing or transcriptional activity. The interdependence of these distinct chromatin features on the linear deoxyribonucleic acid (DNA) sequence precludes a simple dissection of these parameters with respect to their importance for the reorganization of the linear DNA organization into the distinct radial chromatin arrangements observed in the nuclear space. To analyze this problem, we generated probe sets of pooled bacterial artificial chromosome (BAC) clones from HSA 11, 12, 18, and 19 representing R/G-band-assigned chromatin, segments with different gene density and gene loci with different expression levels. Using multicolor 3D flourescent in situ hybridization (FISH) and 3D image analysis, we determined their localization in the nucleus and their positions within or outside the corresponding chromosome territory (CT). For each BAC data on local gene density within 2- and 10-Mb windows, as well as GC (guanine and cytosine) content, replication timing and expression levels were determined. A correlation analysis of these parameters with nuclear positioning revealed regional gene density as the decisive parameter determining the radial positioning of chromatin in the nucleus in contrast to band assignment, replication timing, and transcriptional activity. We demonstrate a polarized distribution of gene-dense vs gene-poor chromatin within CTs with respect to the nuclear border. Whereas we confirm previous reports that a particular gene-dense and transcriptionally highly active region of about 2 Mb on 11p15.5 often loops out from the territory surface, gene-dense and highly expressed sequences were not generally found preferentially at the CT surface as previously suggested.

Keywords

Bacterial Artificial Chromosome Bacterial Artificial Chromosome Clone Gene Density Replication Timing Chromosome Territory 
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.

Abbreviations

3D

three-dimensional

2D

two-dimensional

ARD-NB

average relative distances to the nuclear border

CT

chromosome territory

CT-IC

chromosome territory-interchromatin compartment

D)

relative distance difference

(e)ADS

(enhanced) Absolute 3D distances to surface

G-band

giemsa dark band

Hfb

human fibroblasts

Hly

human (B- and T-) lymphocytes

HSA

homo sapiens chromosome

M-FISH

Multicolor fluorescence in situ hybridization

R-band

giemsa light (reverse) band

RIDGEs

regions of increased gene expression

Notes

Acknowledgments

We gratefully acknowledge very helpful discussions and technical support from Christian Lanctôt, Stefan Müller, Heiner Albiez, and Boris Joffe from our group. We thank C. Cremer for supporting JvH from his funding. We are grateful to Thomas Ried, NCI, Bethesda, MD, for generously providing us BAC-DNA from clones of chromosomes 12, 18, and 19. This work was supported by the Wilhelm-Sanderstiftung (2001.079.2) to TC and MRS and by the EU (3D Genome, LSHG-CT-2003-503441) to TC. HF and NPC were supported by the Wellcome Trust.

Supplementary material

412_2007_98_MOESM1_ESM.doc (1.5 mb)
Figure S1 Gene-density of chromosomes 12, 18, and 19 (DOC 1 527 808 kb)
412_2007_98_MOESM2_ESM.doc (1.1 mb)
Figure S2 Influence of the pepsin treatment on the detektion of Ki67 in Hfb nuclei (DOC 1 111 040 kb)
412_2007_98_MOESM3_ESM.doc (202 kb)
Table 1–8 Overview of all BAC-pools and detailed description of BACs used in this study with the following information (DOC 206 848 kb)

References

  1. Alexandrova O, Solovei I, Cremer T, David CN (2003) Replication labeling patterns and chromosome territories typical of mammalian nuclei are conserved in the early metazoan Hydra. Chromosoma 112:190–200PubMedCrossRefGoogle Scholar
  2. Bartova E, Kozubek S (2006) Nuclear architecture in the light of gene expression and cell differentiation studies. Biol Cell 98:323–336PubMedCrossRefGoogle Scholar
  3. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D (2004) Ultraconserved elements in the human genome. Science 304:1321–1325PubMedCrossRefGoogle Scholar
  4. Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, Muller S, Eils R, Cremer C, Speicher MR, Cremer T (2005) Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol 3:e157PubMedCrossRefGoogle Scholar
  5. Boyle S, Gilchrist S, Bridger JM, Mahy NL, Ellis JA, Bickmore WA (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum Mol Genet 10:211–219PubMedCrossRefGoogle Scholar
  6. Bridger JM, Boyle S, Kill IR, Bickmore WA (2000) Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts. Curr Biol 10:149–152PubMedCrossRefGoogle Scholar
  7. Brown JM, Leach J, Reittie JE, Atzberger A, Lee-Prudhoe J, Wood WG, Higgs DR, Iborra FJ, Buckle VJ (2006) Coregulated human globin genes are frequently in spatial proximity when active. J Cell Biol 172:177–187PubMedCrossRefGoogle Scholar
  8. Caron H, van Schaik B, van der Mee M, Baas F, Riggins G, van Sluis P, Hermus MC, van Asperen R, Boon K, Voute PA, Heisterkamp S, van Kampen A, Versteeg R (2001) The human transcriptome map: clustering of highly expressed genes in chromosomal domains. Science 291:1289–1292PubMedCrossRefGoogle Scholar
  9. Chambeyron S, Bickmore WA (2004) Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev 18:1119–1130PubMedCrossRefGoogle Scholar
  10. Chambeyron S, Da Silva NR, Lawson KA, Bickmore WA (2005) Nuclear re-organisation of the Hoxb complex during mouse embryonic development. Development 132:2215–2223PubMedCrossRefGoogle Scholar
  11. Chuang CH, Carpenter AE, Fuchsova B, Johnson T, de Lanerolle P, Belmont AS (2006) Long-range directional movement of an interphase chromosome site. Curr Biol 16:825–831PubMedCrossRefGoogle Scholar
  12. Claussen U (2005) Chromosomics. Cytogenet Genome Res 111:101–106PubMedCrossRefGoogle Scholar
  13. Clemson CM, Hall LL, Byron M, McNeil J, Lawrence JB (2006) The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences. Proc Natl Acad Sci USA 103:7688–7693PubMedCrossRefGoogle Scholar
  14. Craig JM, Bickmore WA (1993) Chromosome bands—flavours to savour. BioEssays 15:349–354PubMedCrossRefGoogle Scholar
  15. Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301PubMedCrossRefGoogle Scholar
  16. Cremer T, Cremer C (2006) Rise, fall and resurrection of chromosome territories: a historical perspective Part II. Fall and resurrection of chromosome territories during the 1950s to 1980s. Part III. Chromosome territories and the functional nuclear architecture: experiments and models from the 1990s to the present. Eur J Histochem 50:223–272PubMedGoogle Scholar
  17. Cremer M, von Hase J, Volm T, Brero A, Kreth G, Walter J, Fischer C, Solovei I, Cremer C, Cremer T (2001b) Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells. Chromosome Res 9:541–567PubMedCrossRefGoogle Scholar
  18. Cremer M, Kupper K, Wagler B, Wizelman L, von Hase J, Weiland Y, Kreja L, Diebold J, Speicher MR, Cremer T (2003) Inheritance of gene density-related higher order chromatin arrangements in normal and tumor cell nuclei. J Cell Biol 162:809–820PubMedCrossRefGoogle Scholar
  19. Cremer T, Kupper K, Dietzel S, Fakan S (2004) Higher order chromatin architecture in the cell nucleus: on the way from structure to function. Biol Cell 96:555–567PubMedCrossRefGoogle Scholar
  20. Cremer T, Cremer M, Dietzel S, Muller S, Solovei I, Fakan S (2006a) Chromosome territories—a functional nuclear landscape. Curr Opin Cell Biol 18:307–316PubMedCrossRefGoogle Scholar
  21. Cremer M, Weierich C, Solovei I (2006b) Epigenetics protocols database: multicolor 3D-FISH in vertebrate cells. edited by the epigenome network of excellence. http://www.epigenome-noe.net/researchtools/protocols.php
  22. Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA (1999) Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol 145:1119–1131PubMedCrossRefGoogle Scholar
  23. Dietzel S, Schiebel K, Little G, Edelmann P, Rappold GA, Eils R, Cremer C, Cremer T (1999) The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity [in process citation]. Exp Cell Res 252:363–375PubMedCrossRefGoogle Scholar
  24. Eyre-Walker A, Hurst LD (2001) The evolution of isochores. Nat Rev Genet 2:549–555PubMedCrossRefGoogle Scholar
  25. Federico C, Scavo C, Cantarella CD, Motta S, Saccone S, Bernardi G (2006) Gene-rich and gene-poor chromosomal regions have different locations in the interphase nuclei of cold-blooded vertebrates. Chromosoma 115:123–128PubMedCrossRefGoogle Scholar
  26. Fiegler H, Carr P, Douglas EJ, Burford DC, Hunt S, Scott CE, Smith J, Vetrie D, Gorman P, Tomlinson IP, Carter NP (2003) DNA microarrays for comparative genomic hybridization based on DOP-PCR amplification of BAC and PAC clones. Genes Chromosomes Cancer 36:361–374PubMedCrossRefGoogle Scholar
  27. Fiegler H, Redon R, Andrews D, Scott C, Andrews R, Carder C, Clark R, Dovey O, Ellis P, Feuk L, Hunt P, Kalaitzopoulos D, Larkin J, Montgomery L, Perry GH, Plumb BW, Porter K, Rigby RE, Rigler D, Valesia A, Langford C, Humphray SW, Scherer SW, Lee C, Hurles ME, Carter NP (2006) Accurate and reliable high-throughput detection of copy number variation in the human genome. Genome Res 16:1566–1574PubMedCrossRefGoogle Scholar
  28. Foster HA, Bridger JM (2005) The genome and the nucleus: a marriage made by evolution. Genome organisation and nuclear architecture. Chromosoma 114:212–229PubMedCrossRefGoogle Scholar
  29. Francke U (1994) Digitized and differentially shaded human chromosome ideograms for genomic applications. Cytogenet Cell Genet 65:206–218PubMedGoogle Scholar
  30. Furey TS, Haussler D (2003) Integration of the cytogenetic map with the draft human genome sequence. Hum Mol Genet 12:1037–1044PubMedCrossRefGoogle Scholar
  31. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMedGoogle Scholar
  32. Gilbert N, Boyle S, Fiegler H, Woodfine K, Carter NP, Bickmore WA (2004) Chromatin architecture of the human genome: gene-rich domains are enriched in open chromatin fibers. Cell 118:555–566PubMedCrossRefGoogle Scholar
  33. Gilbert N, Gilchrist S, Bickmore WA (2005) Chromatin organization in the mammalian nucleus. Int Rev Cytol 242:283–336PubMedCrossRefGoogle Scholar
  34. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez G, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM (2004) The DNA sequence and biology of human chromosome 19. Nature 428:529–535PubMedCrossRefGoogle Scholar
  35. Gruenbaum Y, Margalit A, Goldman RD, Shumaker DK, Wilson KL (2005) The nuclear lamina comes of age. Nat Rev Mol Cell Biol 6:21–31PubMedCrossRefGoogle Scholar
  36. Habermann FA, Cremer M, Walter J, Kreth G, von Hase J, Bauer K, Wienberg J, Cremer J, Cremer T, Solovei I (2001) Arrangements of macro- and microchromosomes in chicken cells. Chromosome Res 9:569–584PubMedCrossRefGoogle Scholar
  37. Holmquist G, Gray M, Porter T, Jordan J (1982) Characterization of Giemsa dark-and light-band DNA. Cell 31:121–129PubMedCrossRefGoogle Scholar
  38. Kosak ST, Groudine M (2004) Form follows function: the genomic organization of cellular differentiation. Genes Dev 18:1371–1384PubMedCrossRefGoogle Scholar
  39. Kurz A, Lampel S, Nickolenko JE, Bradl J, Benner A, Zirbel RM, Cremer T, Lichter P (1996) Active and inactive genes localize preferentially in the periphery of chromosome territories. J Cell Biol 135:1195–1205PubMedCrossRefGoogle Scholar
  40. Lanctot C, Cheutin T, Cremer M, Cavalli G, Cremer T (2007) Dynamic genome architecture and the regulation of gene expression. Nat Rev Genet 8:104–115PubMedCrossRefGoogle Scholar
  41. Lehrer H, Weise A, Michel S, Starke H, Mrasek K, Heller A, Kuechler A, Claussen U, Liehr T (2004) The hierarchically organized splitting of chromosome bands into sub-bands analyzed by multicolor banding (MCB). Cytogenet Genome Res 105:25–28PubMedCrossRefGoogle Scholar
  42. Lemke J, Claussen J, Michel S, Chudoba I, Muhlig P, Westermann M, Sperling K, Rubtsov N, Grummt UW, Ullmann P, Kromeyer-Hauschild K, Liehr T, Claussen U (2002) The DNA-based structure of human chromosome 5 in interphase. Am J Hum Genet 71:1051–1059PubMedCrossRefGoogle Scholar
  43. Lukasova E, Kozubek S, Kozubek M, Falk M, Amrichova J (2002) The 3D structure of human chromosomes in cell nuclei. Chromosome Res 10:535–548PubMedCrossRefGoogle Scholar
  44. Lukasova E, Kozubek S, Falk M, Kozubek M, Zaloudik J, Vagunda V, Pavlovsky Z (2004) Topography of genetic loci in the nuclei of cells of colorectal carcinoma and adjacent tissue of colonic epithelium. Chromosoma 112:221–230PubMedCrossRefGoogle Scholar
  45. 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 159:753–763PubMedCrossRefGoogle Scholar
  46. Maraldi NM, Squarzoni S, Sabatelli P, Capanni C, Mattioli E, Ognibene A, Lattanzi G (2005) Laminopathies: involvement of structural nuclear proteins in the pathogenesis of an increasing number of human diseases. J Cell Physiol 203:319–327PubMedCrossRefGoogle Scholar
  47. Misteli T (2004) Spatial positioning; a new dimension in genome function. Cell 119:153–156PubMedCrossRefGoogle Scholar
  48. Murmann AE, Gao J, Encinosa M, Gautier M, Peter ME, Eils R, Lichter P, Rowley JD (2005) Local gene density predicts the spatial position of genetic loci in the interphase nucleus. Exp Cell Res 311:14–26, 311:14–26PubMedCrossRefGoogle Scholar
  49. Neusser M, Schubel V, Koch A, Cremer T, Mueller S (2007) Comparative analysis of the three-dimensional genome architecture in interphase nuclei of primates. Chromosoma. DOI  10.1007/s00412-007-0099-3
  50. Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O’Leary SB, O’Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES (2005) DNA sequence and analysis of human chromosome 18. Nature 437:551–555PubMedCrossRefGoogle Scholar
  51. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, Fraser P (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36:1065–1071PubMedCrossRefGoogle Scholar
  52. Parada LA, Sotiriou S, Misteli T (2004) Spatial genome organization. Exp Cell Res 296:64–70PubMedCrossRefGoogle Scholar
  53. Pederson T (2004) The spatial organization of the genome in mammalian cells. Curr Opin Genet Dev 14:203–209PubMedCrossRefGoogle Scholar
  54. Postberg J, Alexandrova O, Cremer T, Lipps HJ (2005) Exploiting nuclear duality of ciliates to analyse topological requirements for DNA replication and transcription. J Cell Sci 118:3973–3983PubMedCrossRefGoogle Scholar
  55. Ragoczy T, Telling A, Sawado T, Groudine M, Kosak ST (2003) A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements. Chromosome Res 11:513–525PubMedCrossRefGoogle Scholar
  56. 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 300:169–178PubMedCrossRefGoogle Scholar
  57. Sadoni N, Langer S, Fauth C, Bernardi G, Cremer T, Turner BM, Zink D (1999) Nuclear organization of mammalian genomes. Polar chromosome territories build up functionally distinct higher order compartments. J Cell Biol 146:1211–1226PubMedCrossRefGoogle Scholar
  58. 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
  59. 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 301:266–279PubMedCrossRefGoogle Scholar
  60. Shopland LS, Johnson CV, Byron M, McNeil J, Lawrence JB (2003) Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods. J Cell Biol 162:981–990PubMedCrossRefGoogle Scholar
  61. Shopland LS, Lynch CR, Peterson KA, Thornton K, Kepper N, Hase J, Stein S, Vincent S, Molloy KR, Kreth G, Cremer C, Bult CJ, O’Brien TP (2006) Folding and organization of a contiguous chromosome region according to the gene distribution pattern in primary genomic sequence. J Cell Biol 174:27–38PubMedCrossRefGoogle Scholar
  62. Simonis M, Klous P, Splinter E, Moshkin Y, Willemsen R, de Wit E, van Steensel B, de Laat W (2006) Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat GenetGoogle Scholar
  63. Singer GA, Lloyd AT, Huminiecki LB, Wolfe KH (2005) Clusters of co-expressed genes in mammalian genomes are conserved by natural selection. Mol Biol Evol 22:767–775PubMedCrossRefGoogle Scholar
  64. Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA (2005) Interchromosomal associations between alternatively expressed loci. Nature 435:637–645PubMedCrossRefGoogle Scholar
  65. Sproul D, Gilbert N, Bickmore WA (2005) The role of chromatin structure in regulating the expression of clustered genes. Nat Rev Genet 6:775–781PubMedCrossRefGoogle Scholar
  66. Tanabe H, Muller S, Neusser M, von Hase J, Calcagno E, Cremer M, Solovei I, Cremer C, Cremer T (2002) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proc Natl Acad Sci USA 99:4424–4429PubMedCrossRefGoogle Scholar
  67. Tumbar T, Belmont AS (2001) Interphase movements of a DNA chromosome region modulated by VP16 transcriptional activator. Nat Cell Biol 3:134–139PubMedCrossRefGoogle Scholar
  68. van Driel R, Fransz PF, Verschure PJ (2003) The eukaryotic genome: a system regulated at different hierarchical levels. J Cell Sci 116:4067–4075PubMedCrossRefGoogle Scholar
  69. Versteeg R, van Schaik BD, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, van Kampen AH (2003) The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Res 13:1998–2004PubMedCrossRefGoogle Scholar
  70. Vinogradov AE (2003) DNA helix: the importance of being GC-rich. Nucleic Acids Res 31:1838–1844PubMedCrossRefGoogle Scholar
  71. Volpi EV, Chevret E, Jones T, Vatcheva R, Williamson J, Beck S, Campbell RD, Goldsworthy M, Powis SH, Ragoussis J, Trowsdale J, Sheer D (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(Pt 9):1565–1576PubMedGoogle Scholar
  72. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Emes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigo R, Guyer M, Hardison RC, Haussler D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562PubMedCrossRefGoogle Scholar
  73. White EJ, Emanuelsson O, Scalzo D, Royce T, Kosak S, Oakeley EJ, Weissman EJ, Gerstein M, Groudine M, Snyder M, Schubeler D (2004) DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states. Proc Natl Acad Sci USA 101:17771–17776PubMedCrossRefGoogle Scholar
  74. Williams RR (2003) Transcription and the territory: the ins and outs of gene positioning. Trends Genet 19:298–302PubMedCrossRefGoogle Scholar
  75. 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 272:163–175PubMedCrossRefGoogle Scholar
  76. Woodfine K, Fiegler H, Beare DM, Collins JE, McCann OT, Young BD, Debernardi S, Mott R, Dunham I, Carter NP (2004) Replication timing of the human genome. Hum Mol Genet 13:191–202PubMedCrossRefGoogle Scholar
  77. Wurtele H, Chartrand P (2006) Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended chromosome conformation capture methodology. Chromosome Res 14:445–477CrossRefGoogle Scholar
  78. Zhao Z, Tavoosidana G, Sjolinder M, Gondor A, Mariano P, Wang S, Kanduri C, Lezcano M, Singh Sandhu K, Singh U, Pant V, Tiwari V, Kurukuti S, Ohlsson R (2006) Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet 38:1341–1347PubMedCrossRefGoogle Scholar
  79. Zink D (2006) The temporal program of DNA replication: new insights into old questions. Chromosoma 115:273–287PubMedCrossRefGoogle Scholar
  80. Zink D, Amaral MD, Englmann A, Lang S, Clarke LA, Rudolph C, Alt F, Luther K, Braz C, Sadoni N, Rosenecker J, Schindelhauer D (2004) Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei. J Cell Biol 166:815–825PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Katrin Küpper
    • 1
  • Alexandra Kölbl
    • 1
  • Dorothee Biener
    • 1
  • Sandra Dittrich
    • 1
  • Johann von Hase
    • 2
  • Tobias Thormeyer
    • 1
  • Heike Fiegler
    • 3
  • Nigel P. Carter
    • 3
  • Michael R. Speicher
    • 4
  • Thomas Cremer
    • 1
  • Marion Cremer
    • 1
  1. 1.Department of Biology II, Anthropology and Human GeneticsLudwig Maximilians UniversityMunichGermany
  2. 2.Kirchhoff Institute for PhysicsUniversity of HeidelbergHeidelbergGermany
  3. 3.The Wellcome Trust Sanger Institute, Wellcome Trust Genome CampusCambridgeUK
  4. 4.Institute of Medical Biology and Human GeneticsMedical University of GrazGrazAustria

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