Chromosoma

, Volume 118, Issue 1, pp 25–36

Chromatin domains in higher eukaryotes: insights from genome-wide mapping studies

Review

Abstract

In genomes of higher eukaryotes, adjacent genes often show coordinated regulation of their expression. Compartmentalization of multiple neighboring genes into a shared chromatin environment can facilitate this coordinated expression. New mapping techniques have begun to reveal that such multigene chromatin domains are a common feature of fly and mammalian genomes. Many different types of chromatin domains have been identified based on the genomic binding patterns of various proteins and histone modifications. In addition, maps of genome–nuclear lamina associations and of looping interactions between loci provide the first systematic views of the three-dimensional folding of interphase chromosomes. These genome-wide datasets uncover new architectural principles of eukaryotic genomes and indicate that multigene chromatin domains are prevalent and important regulatory units.

References

  1. Akhtar A, Gasser SM (2007) The nuclear envelope and transcriptional control. Nat Rev 8:507–517Google Scholar
  2. Beisel C, Buness A, Roustan-Espinosa IM, Koch B, Schmitt S, Haas SA, Hild M, Katsuyama T, Paro R (2007) Comparing active and repressed expression states of genes controlled by the Polycomb/Trithorax group proteins. Proc Natl Acad Sci U S A 104:16615–16620PubMedGoogle Scholar
  3. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412PubMedGoogle Scholar
  4. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–326PubMedGoogle Scholar
  5. 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 biology 3:e157PubMedGoogle Scholar
  6. Boutanaev AM, Kalmykova AI, Shevelyov YY, Nurminsky DI (2002) Large clusters of co-expressed genes in the Drosophila genome. Nature 420:666–669PubMedGoogle Scholar
  7. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, Bell GW, Otte AP, Vidal M, Gifford DK, Young RA, Jaenisch R (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441:349–353PubMedGoogle Scholar
  8. Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K (2006) Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 20:1123–1136PubMedGoogle Scholar
  9. 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 (New York, NY) 291:1289–1292Google Scholar
  10. Cleard F, Moshkin Y, Karch F, Maeda RK (2006) Probing long-distance regulatory interactions in the Drosophila melanogaster bithorax complex using dam identification. Nat Genet 38:931–935PubMedGoogle Scholar
  11. Crawford GE, Davis S, Scacheri PC, Renaud G, Halawi MJ, Erdos MR, Green R, Meltzer PS, Wolfsberg TG, Collins FS (2006) DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nat Methods 3:503–509PubMedGoogle Scholar
  12. Csink AK, Henikoff S (1996) Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature 381:529–531PubMedGoogle Scholar
  13. de Laat W, Klous P, Kooren J, Noordermeer D, Palstra RJ, Simonis M, Splinter E, Grosveld F (2008) Three-dimensional organization of gene expression in erythroid cells. Curr Topics Dev Biol 82:117–139Google Scholar
  14. Dernburg AF, Broman KW, Fung JC, Marshall WF, Philips J, Agard DA, Sedat JW (1996) Perturbation of nuclear architecture by long-distance chromosome interactions. Cell 85:745–759PubMedGoogle Scholar
  15. de Wit E, Greil F, van Steensel B (2005) Genome-wide HP1 binding in Drosophila: developmental plasticity and genomic targeting signals. Genome Res 15:1265–1273PubMedGoogle Scholar
  16. de Wit E, Greil F, van Steensel B (2007) High-resolution mapping reveals links of HP1 with active and inactive chromatin components. PLoS Genet 3:e38PubMedGoogle Scholar
  17. de Wit E, Braunschweig U, Greil F, Bussemaker HJ, van Steensel B (2008) Global chromatin domain organization of the Drosophila genome. PLoS Genet 4:e1000045PubMedGoogle Scholar
  18. Divina P, Vlcek C, Strnad P, Paces V, Forejt J (2005) Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order. BMC Genom 6:29Google Scholar
  19. Dorer DR, Henikoff S (1994) Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila. Cell 77:993–1002PubMedGoogle Scholar
  20. Dorus S, Busby SA, Gerike U, Shabanowitz J, Hunt DF, Karr TL (2006) Genomic and functional evolution of the Drosophila melanogaster sperm proteome. Nature Genet 38:1440–1445PubMedGoogle Scholar
  21. Dostie J, Richmond TA, Arnaout RA, Selzer RR, Lee WL, Honan TA, Rubio ED, Krumm A, Lamb J, Nusbaum C, Green RD, Dekker J (2006) Chromosome conformation capture carbon copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res 16:1299–1309PubMedGoogle Scholar
  22. Duboule D (2007) The rise and fall of Hox gene clusters. Development (Cambridge, England) 134:2549–2560Google Scholar
  23. Ebert A, Lein S, Schotta G, Reuter G (2006) Histone modification and the control of heterochromatic gene silencing in Drosophila. Chrom Res 14:377–392PubMedGoogle Scholar
  24. Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E, Perry P, Ylstra B, Chubb JR, Bickmore WA (2008) Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4:e1000039PubMedGoogle Scholar
  25. Fischer G, Rocha EP, Brunet F, Vergassola M, Dujon B (2006) Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages. PLoS Genet 2:e32PubMedGoogle Scholar
  26. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S (2003) Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 17:1870–1881PubMedGoogle Scholar
  27. Gierman HJ, Indemans MH, Koster J, Goetze S, Seppen J, Geerts D, van Driel R, Versteeg R (2007) Domain-wide regulation of gene expression in the human genome. Genome Res 17:1286–1295PubMedGoogle Scholar
  28. 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 118:555–566PubMedGoogle Scholar
  29. Greil F, van der Kraan I, Delrow J, Smothers JF, de Wit E, Bussemaker HJ, van Driel R, Henikoff S, van Steensel B (2003) Distinct HP1 and Su(var)3–9 complexes bind to sets of developmentally coexpressed genes depending on chromosomal location. Genes Dev 17:2825–2838PubMedGoogle Scholar
  30. Greil F, Moorman C, van Steensel B (2006) DamID: mapping of in vivo protein–genome interactions using tethered DNA adenine methyltransferase. Methods Enzymol 410:342–359PubMedGoogle Scholar
  31. Greil F, de Wit E, Bussemaker HJ, van Steensel B (2007) HP1 controls genomic targeting of four novel heterochromatin proteins in Drosophila. EMBO J 26:741–751PubMedGoogle Scholar
  32. Grewal SI, Elgin SC (2002) Heterochromatin: new possibilities for the inheritance of structure. Curr Opin Genet Dev 12:178–187PubMedGoogle Scholar
  33. Grimaud C, Negre N, Cavalli G (2006) From genetics to epigenetics: the tale of Polycomb group and trithorax group genes. Chrom Res 14:363–375PubMedGoogle Scholar
  34. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W, van Steensel B (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948–951PubMedGoogle Scholar
  35. Han L, Lee DH, Szabo PE (2008) CTCF is the master organizer of domain-wide allele-specific chromatin at the H19/Igf2 imprinted region. Mol Cell Biol 28:1124–1135PubMedGoogle Scholar
  36. Haynes KA, Caudy AA, Collins L, Elgin SC (2006) Element 1360 and RNAi components contribute to HP1-dependent silencing of a pericentric reporter. Curr Biol 16:2222–2227PubMedGoogle Scholar
  37. Hediger F, Gasser SM (2006) Heterochromatin protein 1: don’t judge the book by its cover!. Curr Opin Genet Dev 16:143–150PubMedGoogle Scholar
  38. Heessen S, Fornerod M (2007) The inner nuclear envelope as a transcription factor resting place. EMBO Rep 8:914–919PubMedGoogle Scholar
  39. Hentges KE, Pollock DD, Liu B, Justice MJ (2007) Regional variation in the density of essential genes in mice. PLoS Genet 3:e72PubMedGoogle Scholar
  40. Holohan EE, Kwong C, Adryan B, Bartkuhn M, Herold M, Renkawitz R, Russell S, White R (2007) CTCF genomic binding sites in Drosophila and the organisation of the bithorax complex. PLoS Genet 3:e112PubMedGoogle Scholar
  41. Hurst LD, Williams EJ, Pal C (2002) Natural selection promotes the conservation of linkage of co-expressed genes. Trends Genet 18:604–606PubMedGoogle Scholar
  42. Hurst LD, Pal C, Lercher MJ (2004) The evolutionary dynamics of eukaryotic gene order. Nature Rev 5:299–310Google Scholar
  43. James TC, Elgin SC (1986) Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene. Mol Cell Biol 6:3862–3872PubMedGoogle Scholar
  44. Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH, Spector DL (2004) From silencing to gene expression: real-time analysis in single cells. Cell 116:683–698PubMedGoogle Scholar
  45. Jiang H, Peterlin BM (2008) Differential chromatin looping regulates CD4 expression in immature thymocytes. Mol Cell Biol 28:907–912PubMedGoogle Scholar
  46. Johansson AM, Stenberg P, Pettersson F, Larsson J (2007) POF and HP1 bind expressed exons, suggesting a balancing mechanism for gene regulation. PLoS Genet 3:e209PubMedGoogle Scholar
  47. Kalmykova AI, Nurminsky DI, Ryzhov DV, Shevelyov YY (2005) Regulated chromatin domain comprising cluster of co-expressed genes in Drosophila melanogaster. Nucleic Acids Res 33:1435–1444PubMedGoogle Scholar
  48. Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P, Ahringer J (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231–237PubMedGoogle Scholar
  49. Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H (2002) Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science (New York, NY) 296:158–162Google Scholar
  50. Kosak ST, Scalzo D, Alworth SV, Li F, Palmer S, Enver T, Lee JS, Groudine M (2007) Coordinate gene regulation during hematopoiesis is related to genomic organization. PLoS Biol 5:e309PubMedGoogle Scholar
  51. Kumaran RI, Spector DL (2008) A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180:51–65PubMedGoogle Scholar
  52. Kumaran RI, Thakar R, Spector DL (2008) Chromatin dynamics and gene positioning. Cell 132:929–934PubMedGoogle Scholar
  53. Lanctot C, Cheutin T, Cremer M, Cavalli G, Cremer T (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Rev 8:104–115Google Scholar
  54. Lanzuolo C, Roure V, Dekker J, Bantignies F, Orlando V (2007) Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex. Nature Cell Biol 9:1167–1174PubMedGoogle Scholar
  55. Lee JM, Sonnhammer EL (2003) Genomic gene clustering analysis of pathways in eukaryotes. Genome Res 13:875–882PubMedGoogle Scholar
  56. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, Koseki H, Fuchikami T, Abe K, Murray HL, Zucker JP, Yuan B, Bell GW, Herbolsheimer E, Hannett NM, Sun K, Odom DT, Otte AP, Volkert TL, Bartel DP, Melton DA, Gifford DK, Jaenisch R, Young RA (2006) Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125:301–313PubMedGoogle Scholar
  57. Lifton RP, Goldberg ML, Karp RW, Hogness DS (1978) The organization of the histone genes in Drosophila melanogaster: functional and evolutionary implications. Cold Spring Harb Symp Quant Biol 42(Pt 2):1047–1051PubMedGoogle Scholar
  58. MacAlpine DM, Bell SP (2005) A genomic view of eukaryotic DNA replication. Chrom Res 13:309–326PubMedGoogle Scholar
  59. Mavrich TN, Jiang C, Ioshikhes IP, Li X, Venters BJ, Zanton SJ, Tomsho LP, Qi J, Glaser RL, Schuster SC, Gilmour DS, Albert I, Pugh BF (2008) Nucleosome organization in the Drosophila genome. Nature 453:358–362PubMedGoogle Scholar
  60. Miller MA, Cutter AD, Yamamoto I, Ward S, Greenstein D (2004) Clustered organization of reproductive genes in the C. elegans genome. Curr Biol 14:1284–1290PubMedGoogle Scholar
  61. Misteli T (2007) Beyond the sequence: cellular organization of genome function. Cell 128:787–800PubMedGoogle Scholar
  62. Negre N, Hennetin J, Sun LV, Lavrov S, Bellis M, White KP, Cavalli G (2006) Chromosomal distribution of PcG proteins during Drosophila development. PLoS Biol 4:e170PubMedGoogle Scholar
  63. O’Geen H, Squazzo SL, Iyengar S, Blahnik K, Rinn JL, Chang HY, Green R, Farnham PJ (2007) Genome-wide analysis of KAP1 binding suggests autoregulation of KRAB-ZNFs. PLoS Genet 3:e89PubMedGoogle Scholar
  64. Palstra RJ, Tolhuis B, Splinter E, Nijmeijer R, Grosveld F, de Laat W (2003) The beta-globin nuclear compartment in development and erythroid differentiation. Nat Genet 35:190–194PubMedGoogle Scholar
  65. Palstra RJ, Simonis M, Klous P, Brasset E, Eijkelkamp B, de Laat W (2008) Maintenance of long-range DNA interactions after inhibition of ongoing RNA polymerase II transcription. PLoS ONE 3:e1661PubMedGoogle Scholar
  66. Parada LA, McQueen PG, Misteli T (2004) Tissue-specific spatial organization of genomes. Genome Biol 5:R44PubMedGoogle Scholar
  67. Pickersgill H, Kalverda B, de Wit E, Talhout W, Fornerod M, van Steensel B (2006) Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet 38:1005–1014PubMedGoogle Scholar
  68. Reddy KL, Zullo JM, Bertolino E, Singh H (2008) Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452:243–247PubMedGoogle Scholar
  69. Ren XY, Fiers MW, Stiekema WJ, Nap JP (2005) Local coexpression domains of two to four genes in the genome of Arabidopsis. Plant Physiol 138:923–934PubMedGoogle Scholar
  70. Ringrose L (2007) Polycomb comes of age: genome-wide profiling of target sites. Curr Opin Cell Biol 19:290–297PubMedGoogle Scholar
  71. Roy PJ, Stuart JM, Lund J, Kim SK (2002) Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans. Nature 418:975–979PubMedGoogle Scholar
  72. Sabo PJ, Kuehn MS, Thurman R, Johnson BE, Johnson EM, Cao H, Yu M, Rosenzweig E, Goldy J, Haydock A, Weaver M, Shafer A, Lee K, Neri F, Humbert R, Singer MA, Richmond TA, Dorschner MO, McArthur M, Hawrylycz M, Green RD, Navas PA, Noble WS, Stamatoyannopoulos JA (2006) Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nat Methods 3:511–518PubMedGoogle Scholar
  73. Schones DE, Cui K, Cuddapah S, Roh TY, Barski A, Wang Z, Wei G, Zhao K (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132:887–898PubMedGoogle Scholar
  74. Schotta G, Ebert A, Krauss V, Fischer A, Hoffmann J, Rea S, Jenuwein T, Dorn R, Reuter G (2002) Central role of Drosophila SU(VAR)3–9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J 21:1121–1131PubMedGoogle Scholar
  75. Schubeler D, Scalzo D, Kooperberg C, van Steensel B, Delrow J, Groudine M (2002) Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing. Nat Genet 32:438–442PubMedGoogle Scholar
  76. Schwartz YB, Pirrotta V (2007) Polycomb silencing mechanisms and the management of genomic programmes. Nat Rev 8:9–22Google Scholar
  77. Schwartz YB, Kahn TG, Nix DA, Li XY, Bourgon R, Biggin M, Pirrotta V (2006) Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet 38:700–705PubMedGoogle Scholar
  78. 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 Genet 38:1348–1354PubMedGoogle Scholar
  79. 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 22:767–775PubMedGoogle Scholar
  80. Somech R, Shaklai S, Geller O, Amariglio N, Simon AJ, Rechavi G, Gal-Yam EN (2005) The nuclear-envelope protein and transcriptional repressor LAP2beta interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. J Cell Sci 118:4017–4025PubMedGoogle Scholar
  81. Sparmann A, van Lohuizen M (2006) Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 6:846–856PubMedGoogle Scholar
  82. Spellman PT, Rubin GM (2002) Evidence for large domains of similarly expressed genes in the Drosophila genome. J Biol 1:5PubMedGoogle Scholar
  83. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9:3273–3297PubMedGoogle Scholar
  84. Sproul D, Gilbert N, Bickmore WA (2005) The role of chromatin structure in regulating the expression of clustered genes. Nat Rev 6:775–781Google Scholar
  85. Squazzo SL, O’Geen H, Komashko VM, Krig SR, Jin VX, Jang SW, Margueron R, Reinberg D, Green R, Farnham PJ (2006) Suz12 binds to silenced regions of the genome in a cell-type-specific manner. Genome Res 16:890–900PubMedGoogle Scholar
  86. Stolc V, Gauhar Z, Mason C, Halasz G, van Batenburg MF, Rifkin SA, Hua S, Herreman T, Tongprasit W, Barbano PE, Bussemaker HJ, White KP (2004) A gene expression map for the euchromatic genome of Drosophila melanogaster. Science (New York, NY) 306:655–660Google Scholar
  87. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A 101:6062–6067PubMedGoogle Scholar
  88. Taddei A, Hediger F, Neumann FR, Gasser SM (2004) The function of nuclear architecture: a genetic approach. Annu Rev Genet 38:305–345PubMedGoogle Scholar
  89. Talbert PB, Henikoff S (2006) Spreading of silent chromatin: inaction at a distance. Nat Rev 7:793–803Google Scholar
  90. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nature Struct Mol Biol 14:1025–1040Google Scholar
  91. Teichmann SA, Veitia RA (2004) Genes encoding subunits of stable complexes are clustered on the yeast chromosomes: an interpretation from a dosage balance perspective. Genetics 167:2121–2125PubMedGoogle Scholar
  92. Tolhuis B, Palstra RJ, Splinter E, Grosveld F, de Laat W (2002) Looping and interaction between hypersensitive sites in the active beta-globin locus. Mol Cell 10:1453–1465PubMedGoogle Scholar
  93. Tolhuis B, de Wit E, Muijrers I, Teunissen H, Talhout W, van Steensel B, van Lohuizen M (2006) Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nat Genet 38:694–699PubMedGoogle Scholar
  94. van Steensel B, Delrow J, Henikoff S (2001) Chromatin profiling using targeted DNA adenine methyltransferase. Nat Genet 27:304–308PubMedGoogle Scholar
  95. 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 13:1998–2004PubMedGoogle Scholar
  96. Vogel MJ, Guelen L, de Wit E, Peric-Hupkes D, Loden M, Talhout W, Feenstra M, Abbas B, Classen AK, van Steensel B (2006) Human heterochromatin proteins form large domains containing KRAB-ZNF genes. Genome Res 16:1493–1504PubMedGoogle Scholar
  97. Wallace JA, Felsenfeld G (2007) We gather together: insulators and genome organization. Curr Opin Genet Dev 17:400–407PubMedGoogle Scholar
  98. Wang Q, Carroll JS, Brown M (2005) Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell 19:631–642PubMedGoogle Scholar
  99. Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39:457–466PubMedGoogle Scholar
  100. White EJ, Emanuelsson O, Scalzo D, Royce T, Kosak S, Oakeley EJ, Weissman S, 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 U S A 101:17771–17776PubMedGoogle Scholar
  101. 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. Human Mol Genet 13:191–202Google Scholar
  102. Workman JL (2006) Nucleosome displacement in transcription. Genes Dev 20:2009–2017PubMedGoogle Scholar
  103. Yamashita T, Honda M, Takatori H, Nishino R, Hoshino N, Kaneko S (2004) Genome-wide transcriptome mapping analysis identifies organ-specific gene expression patterns along human chromosomes. Genomics 84:867–875PubMedGoogle Scholar
  104. Yasuhara JC, Wakimoto BT (2008) Molecular landscape of modified histones in Drosophila heterochromatic genes and euchromatin–heterochromatin transition zones. PLoS Genet 4:e16PubMedGoogle Scholar
  105. Yi G, Sze SH, Thon MR (2007) Identifying clusters of functionally related genes in genomes. Bioinformatics (Oxford, England) 23:1053–1060Google Scholar
  106. Zhan S, Horrocks J, Lukens LN (2006) Islands of co-expressed neighbouring genes in Arabidopsis thaliana suggest higher-order chromosome domains. Plant J 45:347–357PubMedGoogle Scholar
  107. Zhao Z, Tavoosidana G, Sjolinder M, Gondor A, Mariano P, Wang S, Kanduri C, Lezcano M, Sandhu KS, 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 38:1341–1347PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Division of Gene RegulationNetherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Hubrecht InstituteUtrechtthe Netherlands

Personalised recommendations