Skip to main content
SpringerLink
Log in

Spatial Genome Organization and Disease

  • Chapter
  • First Online:
The Functional Nucleus

Abstract

The nucleus is a complex organelle that performs a wide array of critical functions. Within the nucleus the genome is highly organized. Individual chromosomes form discrete chromosome territories. The organization of the genome is correlated with function, for example gene expression. Each chromosome and gene has a preferential spatial location, which can vary by cell type, differentiation stage and during disease. Active and inactive chromatin tends to be spatially separated both within the 3D nuclear space and within a chromosome territory. The molecular mechanisms that determine genome organization are currently poorly understood. However, it is known that the proximity of gene loci can contribute to translocation partner choice. The recent development of a plethora of new molecular techniques and imaging strategies, combined with fluorescent in situ hybridization, is being applied to both normal and diseased cells. Such studies will bring us closer to understanding the implications of genome organization and the molecules and mechanisms that determine it.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Ballabio E, Cantarella CD, Federico C, Di Mare P, Hall G, Harbott J, Hughes J, Saccone S, Tosi S (2009) Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias. Leukemia 23(6):1179–1182. doi:10.1038/leu.2009.15

    Article  CAS  PubMed  Google Scholar 

  • Bian Q, Khanna N, Alvikas J, Belmont AS (2013) beta-Globin cis-elements determine differential nuclear targeting through epigenetic modifications. J Cell Biol 203(5):767–783. doi:10.1083/jcb.201305027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bickmore WA (2013) The spatial organization of the human genome. Annu Rev Genomics Hum Genet 14:67–84. doi:10.1146/annurev-genom-091212-153515

    Article  CAS  PubMed  Google Scholar 

  • Bickmore WA, Teague P (2002) Influences of chromosome size, gene density and nuclear position on the frequency of constitutional translocations in the human population. Chromosome Res 10(8):707–715

    Article  CAS  PubMed  Google Scholar 

  • Bickmore WA, van Steensel B (2013) Genome architecture: domain organization of interphase chromosomes. Cell 152(6):1270–1284. doi:10.1016/j.cell.2013.02.001

    Article  CAS  PubMed  Google Scholar 

  • Blobel G (1985) Gene gating: a hypothesis. Proc Natl Acad Sci USA 82(24):8527–8529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(5):e157

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Borden J, Manuelidis L (1988) Movement of the X chromosome in epilepsy. Science 242:1687–1691

    Article  CAS  PubMed  Google Scholar 

  • Boutanaev AM, Mikhaylova LM, Nurminsky DI (2005) The pattern of chromosome folding in interphase is outlined by the linear gene density profile. Mol Cell Biol 25(18):8379–8386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(3):211–219

    Article  CAS  PubMed  Google Scholar 

  • Boyle S, Rodesch MJ, Halvensleben HA, Jeddeloh JA, Bickmore WA (2011) Fluorescence in situ hybridization with high-complexity repeat-free oligonucleotide probes generated by massively parallel synthesis. Chromosome Res 19(7):901–909. doi:10.1007/s10577-011-9245-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Branco MR, Pombo A (2006) Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol 4(5), e138

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bridger JM, Boyle S, Kill IR, Bickmore WA (2000) Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts. Curr Biol 10(3):149–152

    Article  CAS  PubMed  Google Scholar 

  • 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(2):177–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown JM, Green J, das Neves RP, Wallace HA, Smith AJ, Hughes J, Gray N, Taylor S, Wood WG, Higgs DR, Iborra FJ, Buckle VJ (2008) Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. J Cell Biol 182(6):1083–1097. doi:10.1083/jcb.200803174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burke B, Stewart CL (2013) The nuclear lamins: flexibility in function. Nat Rev Mol Cell Biol 14(1):13–24. doi:10.1038/nrm3488

    Article  CAS  PubMed  Google Scholar 

  • Cavalli G, Misteli T (2013) Functional implications of genome topology. Nat Struct Mol Biol 20(3):290–299. doi:10.1038/nsmb.2474

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, Park J, Blackburn EH, Weissman JS, Qi LS, Huang B (2013) Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155(7):1479–1491. doi:10.1016/j.cell.2013.12.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, Alt FW (2011) Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147(1):107–119. doi:10.1016/j.cell.2011.07.049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(20):7688–7693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clowney EJ, LeGros MA, Mosley CP, Clowney FG, Markenskoff-Papadimitriou EC, Myllys M, Barnea G, Larabell CA, Lomvardas S (2012) Nuclear aggregation of olfactory receptor genes governs their monogenic expression. Cell 151(4):724–737. doi:10.1016/j.cell.2012.09.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2(4):292–301

    Article  CAS  PubMed  Google Scholar 

  • Cremer T, Cremer M (2010) Chromosome territories. Cold Spring Harb Perspect Biol 2(3):a003889. doi:10.1101/cshperspect.a003889

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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(5):809–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cremer T, Cremer C, Lichter P (2014) Recollections of a scientific journey published in human genetics: from chromosome territories to interphase cytogenetics and comparative genome hybridization. Hum Genet 133(4):403–416. doi:10.1007/s00439-014-1425-5

    Article  PubMed  Google Scholar 

  • 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 145:1119–1131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dekker J, Misteli T (2015) Long-range genome interactions Epigenetics, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • Del Prete S, Arpon J, Sakai K, Andrey P, Gaudin V (2014) Nuclear architecture and chromatin dynamics in interphase nuclei of Arabidopsis thaliana. Cytogenet Genome Res 143(1-3):28–50. doi:10.1159/000363724

    Article  PubMed  Google Scholar 

  • Dellaire G, Kepkay R, Bazett-Jones DP (2009) High resolution imaging of changes in the structure and spatial organization of chromatin, gamma-H2A.X and the MRN complex within etoposide-induced DNA repair foci. Cell Cycle 8(22):3750–3769

    Article  CAS  PubMed  Google Scholar 

  • Demmerle J, Koch AJ, Holaska JM (2013) Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, and Pax7 genes during myogenesis. Chromosome Res 21(8):765–779. doi:10.1007/s10577-013-9381-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dittmer TA, Misteli T (2011) The lamin protein family. Genome Biol 12(5):222. doi:10.1186/gb-2011-12-5-222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398):376–380. doi:10.1038/nature11082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egecioglu D, Brickner JH (2011) Gene positioning and expression. Curr Opin Cell Biol 23(3):338–345. doi:10.1016/j.ceb.2011.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fanucchi S, Shibayama Y, Burd S, Weinberg MS, Mhlanga MM (2013) Chromosomal contact permits transcription between coregulated genes. Cell 155(3):606–620. doi:10.1016/j.cell.2013.09.051

    Article  CAS  PubMed  Google Scholar 

  • Ferrai C, de Castro IJ, Lavitas L, Chotalia M, Pombo A (2010a) Gene positioning. Cold Spring Harb Perspect Biol 2(6):a000588. doi:10.1101/cshperspect.a000588

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ferrai C, Xie SQ, Luraghi P, Munari D, Ramirez F, Branco MR, Pombo A, Crippa MP (2010b) Poised transcription factories prime silent uPA gene prior to activation. PLoS Biol 8(1), e1000270. doi:10.1371/journal.pbio.1000270

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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(3):e1000039

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Foster HA, Griffin DK, Bridger JM (2012) Interphase chromosome positioning in in vitro porcine cells and ex vivo porcine tissues. BMC Cell Biol 13:30. doi:10.1186/1471-2121-13-30

    Article  PubMed  PubMed Central  Google Scholar 

  • Franco S, Gostissa M, Zha S, Lombard DB, Murphy MM, Zarrin AA, Yan C, Tepsuporn S, Morales JC, Adams MM, Lou Z, Bassing CH, Manis JP, Chen J, Carpenter PB, Alt FW (2006) H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Mol Cell 21(2):201–214. doi:10.1016/j.molcel.2006.01.005

    Article  CAS  PubMed  Google Scholar 

  • Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Lobrich M, Jeggo PA (2008) ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 31(2):167–177. doi:10.1016/j.molcel.2008.05.017

    Article  CAS  PubMed  Google Scholar 

  • Groth A, Rocha W, Verreault A, Almouzni G (2007) Chromatin challenges during DNA replication and repair. Cell 128(4):721–733. doi:10.1016/j.cell.2007.01.030

    Article  CAS  PubMed  Google Scholar 

  • 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(7197):948–951. doi:10.1038/nature06947

    Article  CAS  PubMed  Google Scholar 

  • Hacisuleyman E, Goff LA, Trapnell C, Williams A, Henao-Mejia J, Sun L, McClanahan P, Hendrickson DG, Sauvageau M, Kelley DR, Morse M, Engreitz J, Lander ES, Guttman M, Lodish HF, Flavell R, Raj A, Rinn JL (2014) Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nat Struct Mol Biol 21(2):198–206. doi:10.1038/nsmb.2764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haffner MC, Aryee MJ, Toubaji A, Esopi DM, Albadine R, Gurel B, Isaacs WB, Bova GS, Liu W, Xu J, Meeker AK, Netto G, De Marzo AM, Nelson WG, Yegnasubramanian S (2010) Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nat Genet 42(8):668–675. doi:10.1038/ng.613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hakim O, Sung MH, Voss TC, Splinter E, John S, Sabo PJ, Thurman RE, Stamatoyannopoulos JA, de Laat W, Hager GL (2011) Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements. Genome Res 21(5):697–706. doi:10.1101/gr.111153.110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hakim O, Resch W, Yamane A, Klein I, Kieffer-Kwon KR, Jankovic M, Oliveira T, Bothmer A, Voss TC, Ansarah-Sobrinho C, Mathe E, Liang G, Cobell J, Nakahashi H, Robbiani DF, Nussenzweig A, Hager GL, Nussenzweig MC, Casellas R (2012) DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 484(7392):69–74. doi:10.1038/nature10909

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hall LL, Carone DM, Gomez AV, Kolpa HJ, Byron M, Mehta N, Fackelmayer FO, Lawrence JB (2014) Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes. Cell 156(5):907–919. doi:10.1016/j.cell.2014.01.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harewood L, Schutz F, Boyle S, Perry P, Delorenzi M, Bickmore WA, Reymond A (2010) The effect of translocation-induced nuclear reorganization on gene expression. Genome Res 20(5):554–564. doi:10.1101/gr.103622.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hewitt SL, High FA, Reiner SL, Fisher AG, Merkenschlager M (2004) Nuclear repositioning marks the selective exclusion of lineage-inappropriate transcription factor loci during T helper cell differentiation. Eur J Immunol 34(12):3604–3613

    Article  CAS  PubMed  Google Scholar 

  • Hiratani I, Ryba T, Itoh M, Yokochi T, Schwaiger M, Chang CW, Lyou Y, Townes TM, Schübeler D, Gilbert DM (2008) Global reorganization of replication domains during embryonic stem cell differentiation. PLoS Biol 6, e245. doi:10.1371/journal.pbio.0060245

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hoffmann K, Sperling K, Olins AL, Olins DE (2007) The granulocyte nucleus and lamin B receptor: avoiding the ovoid. Chromosoma 116(3):227–235. doi:10.1007/s00412-007-0094-8

    Article  CAS  PubMed  Google Scholar 

  • Khanna N, Hu Y, Belmont AS (2014) HSP70 transgene directed motion to nuclear speckles facilitates heat shock activation. Curr Biol 24(10):1138–1144. doi:10.1016/j.cub.2014.03.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS, Janssen H, Amendola M, Nolen LD, Bickmore WA, van Steensel B (2013) Single-cell dynamics of genome-nuclear lamina interactions. Cell 153(1):178–192. doi:10.1016/j.cell.2013.02.028

    Article  CAS  PubMed  Google Scholar 

  • Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, Casellas R, Nussenzweig MC (2011) Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147(1):95–106. doi:10.1016/j.cell.2011.07.048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knight M, Ittiprasert W, Odoemelam EC, Adema CM, Miller A, Raghavan N, Bridger JM (2011) Non-random organization of the Biomphalaria glabrata genome in interphase Bge cells and the spatial repositioning of activated genes in cells co-cultured with Schistosoma mansoni. Int J Parasitol 41(1):61–70. doi:10.1016/j.ijpara.2010.07.015

    Article  CAS  PubMed  Google Scholar 

  • 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 296(5565):158–162

    Article  CAS  PubMed  Google Scholar 

  • Kruhlak MJ, Celeste A, Dellaire G, Fernandez-Capetillo O, Muller WG, McNally JG, Bazett-Jones DP, Nussenzweig A (2006) Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J Cell Biol 172(6):823–834. doi:10.1083/jcb.200510015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubben N, Adriaens M, Meuleman W, Voncken JW, van Steensel B, Misteli T (2012) Mapping of lamin A- and progerin-interacting genome regions. Chromosoma 121(5):447–464. doi:10.1007/s00412-012-0376-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumaran RI, Spector DL (2008) A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol 180(1):51–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li C, Shi Z, Zhang L, Huang Y, Liu A, Jin Y, Yu Y, Bai J, Chen D, Gendron C, Liu X, Fu S (2010) Dynamic changes of territories 17 and 18 during EBV-infection of human lymphocytes. Mol Biol Rep 37(5):2347–2354. doi:10.1007/s11033-009-9740-y

    Article  CAS  PubMed  Google Scholar 

  • Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326(5950):289–293. doi:10.1126/science.1181369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin C, Yang L, Tanasa B, Hutt K, Ju BG, Ohgi K, Zhang J, Rose DW, Fu XD, Glass CK, Rosenfeld MG (2009) Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell 139(6):1069–1083. doi:10.1016/j.cell.2009.11.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lukasova E, Kozubek S, Kozubek M, Kjeronska J, Ryznar L, Horakova J, Krahulcova E, Horneck G (1997) Localisation and distance between ABL and BCR genes in interphase nuclei of bone marrow cells of control donors and patients with chronic myeloid leukaemia. Hum Genet 100(5-6):525–535

    Article  CAS  PubMed  Google Scholar 

  • Makatsori D, Kourmouli N, Polioudaki H, Shultz LD, McLean K, Theodoropoulos PA, Singh PB, Georgatos SD (2004) The inner nuclear membrane protein lamin B receptor forms distinct microdomains and links epigenetically marked chromatin to the nuclear envelope. J Biol Chem 279(24):25567–25573. doi:10.1074/jbc.M313606200

    Article  CAS  PubMed  Google Scholar 

  • Malhas A, Lee CF, Sanders R, Saunders NJ, Vaux DJ (2007) Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression. J Cell Biol 176(5):593–603. doi:10.1083/jcb.200607054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mani RS, Tomlins SA, Callahan K, Ghosh A, Nyati MK, Varambally S, Palanisamy N, Chinnaiyan AM (2009) Induced chromosomal proximity and gene fusions in prostate cancer. Science 326(5957):1230. doi:10.1126/science.1178124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matarazzo MR, Boyle S, D'Esposito M, Bickmore WA (2007) Chromosome territory reorganization in a human disease with altered DNA methylation. Proc Natl Acad Sci USA 104(42):16546–16551. doi:10.1073/pnas.0702924104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathas S, Kreher S, Meaburn KJ, Johrens K, Lamprecht B, Assaf C, Sterry W, Kadin ME, Daibata M, Joos S, Hummel M, Stein H, Janz M, Anagnostopoulos I, Schrock E, Misteli T, Dorken B (2009) Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma. Proc Natl Acad Sci USA 106(14):5831–5836. doi:10.1073/pnas.0900912106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathur S, Glogowska A, McAvoy E, Righolt C, Rutherford J, Willing C, Banik U, Ruthirakuhan M, Mai S, Garcia A (2014) Three-dimensional quantitative imaging of telomeres in buccal cells identifies mild, moderate, and severe Alzheimer’s disease patients. J Alzheimers Dis 39(1):35–48. doi:10.3233/JAD-130866

    PubMed  Google Scholar 

  • Mattout A, Pike BL, Towbin BD, Bank EM, Gonzalez-Sandoval A, Stadler MB, Meister P, Gruenbaum Y, Gasser SM (2011) An EDMD mutation in C. elegans lamin blocks muscle-specific gene relocation and compromises muscle integrity. Curr Biol 21(19):1603–1614. doi:10.1016/j.cub.2011.08.030

    Article  CAS  PubMed  Google Scholar 

  • McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K (2013) Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res 23(2):260–269. doi:10.1101/gr.138032.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meaburn KJ, Misteli T (2007) Cell biology: chromosome territories. Nature 445(7126):379–781. doi:10.1038/445379a

    Article  CAS  PubMed  Google Scholar 

  • Meaburn KJ, Misteli T (2008) Locus-specific and activity-independent gene repositioning during early tumorigenesis. J Cell Biol 180(1):39–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meaburn KJ, Levy N, Toniolo D, Bridger JM (2005) Chromosome positioning is largely unaffected in lymphoblastoid cell lines containing emerin or A-type lamin mutations. Biochem Soc Trans 33(Pt 6):1438–1440. doi:10.1042/BST20051438

    Article  CAS  PubMed  Google Scholar 

  • Meaburn KJ, Cabuy E, Bonne G, Levy N, Morris GE, Novelli G, Kill IR, Bridger JM (2007a) Primary laminopathy fibroblasts display altered genome organization and apoptosis. Aging Cell 6(2):139–153. doi:10.1111/j.1474-9726.2007.00270.x

    Article  CAS  PubMed  Google Scholar 

  • Meaburn KJ, Misteli T, Soutoglou E (2007b) Spatial genome organization in the formation of chromosomal translocations. Semin Cancer Biol 17(1):80–90. doi:10.1016/j.semcancer.2006.10.008

    Article  CAS  PubMed  Google Scholar 

  • Meaburn KJ, Newbold RF, Bridger JM (2008) Positioning of human chromosomes in murine cell hybrids according to synteny. Chromosoma 117(6):579–591. doi:10.1007/s00412-008-0175-3

    Article  PubMed  Google Scholar 

  • Meaburn KJ, Gudla PR, Khan S, Lockett SJ, Misteli T (2009) Disease-specific gene repositioning in breast cancer. J Cell Biol 187(6):801–812. doi:10.1083/jcb.200909127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehta IS, Amira M, Harvey AJ, Bridger JM (2010) Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts. Genome Biol 11(1):R5. doi:10.1186/gb-2010-11-1-r5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mehta IS, Eskiw CH, Arican HD, Kill IR, Bridger JM (2011) Farnesyltransferase inhibitor treatment restores chromosome territory positions and active chromosome dynamics in Hutchinson-Gilford progeria syndrome cells. Genome Biol 12(8):R74. doi:10.1186/gb-2011-12-8-r74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehta IS, Kulashreshtha M, Chakraborty S, Kolthur-Seetharam U, Rao BJ (2013) Chromosome territories reposition during DNA damage-repair response. Genome Biol 14(12):R135. doi:10.1186/gb-2013-14-12-r135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mewborn SK, Puckelwartz MJ, Abuisneineh F, Fahrenbach JP, Zhang Y, MacLeod H, Dellefave L, Pytel P, Selig S, Labno CM, Reddy K, Singh H, McNally E (2010) Altered chromosomal positioning, compaction, and gene expression with a lamin A/C gene mutation. PLoS One 5(12), e14342. doi:10.1371/journal.pone.0014342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Misteli T (2010) Higher-order genome organization in human disease. Cold Spring Harb Perspect Biol 2(8):a000794. doi:10.1101/cshperspect.a000794

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Morey C, Kress C, Bickmore WA (2009) Lack of bystander activation shows that localization exterior to chromosome territories is not sufficient to up-regulate gene expression. Genome Res 19(7):1184–1194. doi:10.1101/gr.089045.108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murata S, Nakazawa T, Ohno N, Terada N, Iwashina M, Mochizuki K, Kondo T, Nakamura N, Yamane T, Iwasa S, Ohno S, Katoh R (2007) Conservation and alteration of chromosome territory arrangements in thyroid carcinoma cell nuclei. Thyroid 17(6):489–496. doi:10.1089/thy.2006.0328

    Article  CAS  PubMed  Google Scholar 

  • 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(1):14–26

    Article  CAS  PubMed  Google Scholar 

  • Nagai S, Dubrana K, Tsai-Pflugfelder M, Davidson MB, Roberts TM, Brown GW, Varela E, Hediger F, Gasser SM, Krogan NJ (2008) Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 322(5901):597–602. doi:10.1126/science.1162790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neves H, Ramos C, da Silva MG, Parreira A, Parreira L (1999) The nuclear topography of ABL, BCR, PML, and RARalpha genes: evidence for gene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation. Blood 93(4):1197–1207

    CAS  PubMed  Google Scholar 

  • Parada LA, McQueen PG, Munson PJ, Misteli T (2002) Conservation of relative chromosome positioning in normal and cancer cells. Curr Biol 12(19):1692–1697

    Article  CAS  PubMed  Google Scholar 

  • Parada L, McQueen P, Misteli T (2004) Tissue-specific spatial organization of genomes. Genome Biol 7:R44

    Article  Google Scholar 

  • Paz N, Zabala A, Royo F, Garcia-Orad A, Zugaza JL, Parada LA (2013) Combined fluorescent-chromogenic in situ hybridization for identification and laser microdissection of interphase chromosomes. PLoS One 8(4):e60238. doi:10.1371/journal.pone.0060238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, Brugman W, Graf S, Flicek P, Kerkhoven RM, van Lohuizen M, Reinders M, Wessels L, van Steensel B (2010) Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell 38(4):603–613. doi:10.1016/j.molcel.2010.03.016

    Article  CAS  PubMed  Google Scholar 

  • 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(9):1005–1014. doi:10.1038/ng1852

    Article  CAS  PubMed  Google Scholar 

  • Ragoczy T, Bender MA, Telling A, Byron R, Groudine M (2006) The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev 20(11):1447–1457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reddy KL, Zullo JM, Bertolino E, Singh H (2008) Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452(7184):243–247

    Article  CAS  PubMed  Google Scholar 

  • Rieder D, Ploner C, Krogsdam AM, Stocker G, Fischer M, Scheideler M, Dani C, Amri EZ, Muller WG, McNally JG, Trajanoski Z (2014) Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories. Cell Mol Life Sci 71(9):1741–1759. doi:10.1007/s00018-013-1465-3

    Article  CAS  PubMed  Google Scholar 

  • Rocha PP, Micsinai M, Kim JR, Hewitt SL, Souza PP, Trimarchi T, Strino F, Parisi F, Kluger Y, Skok JA (2012) Close proximity to Igh is a contributing factor to AID-mediated translocations. Mol Cell 47(6):873–885. doi:10.1016/j.molcel.2012.06.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roix JJ, McQueen PG, Munson PJ, Parada LA, Misteli T (2003) Spatial proximity of translocation-prone gene loci in human lymphomas. Nat Genet 34(3):287–291

    Article  CAS  PubMed  Google Scholar 

  • Roukos V, Misteli T (2014) The biogenesis of chromosome translocations. Nat Cell Biol 16(4):293–300. doi:10.1038/ncb2941

    Article  CAS  PubMed  Google Scholar 

  • Roukos V, Voss TC, Schmidt CK, Lee S, Wangsa D, Misteli T (2013) Spatial dynamics of chromosome translocations in living cells. Science 341(6146):660–664. doi:10.1126/science.1237150

    Article  CAS  PubMed  Google Scholar 

  • Scaffidi P, Misteli T (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11(4):440–445. doi:10.1038/nm1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS, Eskiw CH, Luo Y, Wei CL, Ruan Y, Bieker JJ, Fraser P (2010) Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat Genet 42(1):53–61. doi:10.1038/ng.496

    Article  CAS  PubMed  Google Scholar 

  • Schotta G, Sengupta R, Kubicek S, Malin S, Kauer M, Callen E, Celeste A, Pagani M, Opravil S, De La Rosa-Velazquez IA, Espejo A, Bedford MT, Nussenzweig A, Busslinger M, Jenuwein T (2008) A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse. Genes Dev 22(15):2048–2061. doi:10.1101/gad.476008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sexton T, Yaffe E, Kenigsberg E, Bantignies F, Leblanc B, Hoichman M, Parrinello H, Tanay A, Cavalli G (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148(3):458–472. doi:10.1016/j.cell.2012.01.010

    Article  CAS  PubMed  Google Scholar 

  • Sharma R, Meister P (2013) Nuclear organization in the nematode C. elegans. Curr Opin Cell Biol 25(3):395–402. doi:10.1016/j.ceb.2013.02.002

    Article  CAS  PubMed  Google Scholar 

  • 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(1):27–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 103(23):8703–8708. doi:10.1073/pnas.0602569103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solovei I, Kreysing M, Lanctot C, Kosem S, Peichl L, Cremer T, Guck J, Joffe B (2009) Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137(2):356–368. doi:10.1016/j.cell.2009.01.052

    Article  CAS  PubMed  Google Scholar 

  • Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M, Cohen TV, Devys D, Foisner R, Peichl L, Herrmann H, Blum H, Engelkamp D, Stewart CL, Leonhardt H, Joffe B (2013) LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152(3):584–598. doi:10.1016/j.cell.2013.01.009

    Article  CAS  PubMed  Google Scholar 

  • Sun HB, Shen J, Yokota H (2000) Size-dependent positioning of human chromosomes in interphase nuclei. Biophys J 79(1):184–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szczerbal I, Bridger JM (2010) Association of adipogenic genes with SC-35 domains during porcine adipogenesis. Chromosome Res 18(8):887–895. doi:10.1007/s10577-010-9176-1

    Article  CAS  PubMed  Google Scholar 

  • Taimen P, Pfleghaar K, Shimi T, Moller D, Ben-Harush K, Erdos MR, Adam SA, Herrmann H, Medalia O, Collins FS, Goldman AE, Goldman RD (2009) A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization. Proc Natl Acad Sci USA 106(49):20788–20793. doi:10.1073/pnas.0911895106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takizawa T, Gudla PR, Guo L, Lockett S, Misteli T (2008a) Allele-specific nuclear positioning of the monoallelically expressed astrocyte marker GFAP. Genes Dev 22(4):489–498. doi:10.1101/gad.1634608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takizawa T, Meaburn KJ, Misteli T (2008b) The meaning of gene positioning. Cell 135(1):9–13. doi:10.1016/j.cell.2008.09.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timme S, Schmitt E, Stein S, Schwarz-Finsterle J, Wagner J, Walch A, Werner M, Hausmann M, Wiech T (2011) Nuclear position and shape deformation of chromosome 8 territories in pancreatic ductal adenocarcinoma. Anal Cell Pathol 34(1–2):21–33. doi:10.3233/ACP-2011-0004

    Article  Google Scholar 

  • Towbin BD, Gonzalez-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, Askjaer P, Gasser SM (2012) Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150(5):934–947. doi:10.1016/j.cell.2012.06.051

    Article  CAS  PubMed  Google Scholar 

  • van Steensel B, Dekker J (2010) Genomics tools for unraveling chromosome architecture. Nat Biotechnol 28(10):1089–1095. doi:10.1038/nbt.1680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wiech T, Timme S, Riede F, Stein S, Schuricke M, Cremer C, Werner M, Hausmann M, Walch A (2005) Human archival tissues provide a valuable source for the analysis of spatial genome organization. Histochem Cell Biol 123(3):229–238. doi:10.1007/s00418-005-0768-3

    Article  CAS  PubMed  Google Scholar 

  • Wiech T, Stein S, Lachenmaier V, Schmitt E, Schwarz-Finsterle J, Wiech E, Hildenbrand G, Werner M, Hausmann M (2009) Spatial allelic imbalance of BCL2 genes and chromosome 18 territories in nonneoplastic and neoplastic cervical squamous epithelium. Eur Biophys J 38(6):793–806

    Article  CAS  PubMed  Google Scholar 

  • Williams RR, Azuara V, Perry P, Sauer S, Dvorkina M, Jorgensen H, Roix J, McQueen P, Misteli T, Merkenschlager M, Fisher AG (2006) Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci 119(Pt 1):132–140

    Article  CAS  PubMed  Google Scholar 

  • Wong X, Luperchio TR, Reddy KL (2014) NET gains and losses: the role of changing nuclear envelope proteomes in genome regulation. Curr Opin Cell Biol 28:105–120. doi:10.1016/j.ceb.2014.04.005

    Article  CAS  PubMed  Google Scholar 

  • Zeitz MJ, Ay F, Heidmann JD, Lerner PL, Noble WS, Steelman BN, Hoffman AR (2013) Genomic interaction profiles in breast cancer reveal altered chromatin architecture. PLoS One 8(9):e73974. doi:10.1371/journal.pone.0073974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, McCord RP, Ho YJ, Lajoie BR, Hildebrand DG, Simon AC, Becker MS, Alt FW, Dekker J (2012) Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 148(5):908–921. doi:10.1016/j.cell.2012.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmer C, Fabre E (2011) Principles of chromosomal organization: lessons from yeast. J Cell Biol 192(5):723–733. doi:10.1083/jcb.201010058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zink D, Amaral MD, Englmann A, Land S, Clarke LA, Rudolph C, Alt F, Luther K, Braz C, Sadoni N, Rosenecker J, Schindelhauer D (2004a) Transcription-dependent spatial arrangement of CFTR and adjacent genes in human cell nuclei. J Cell Biol I166:815–825

    Article  Google Scholar 

  • Zink D, Fische AH, Nickerson JA (2004b) Nuclear structure in cancer cells. Nat Rev Cancer 4(9):677–687

    Article  CAS  PubMed  Google Scholar 

  • Zuleger N, Boyle S, Kelly DA, de Las Heras JI, Lazou V, Korfali N, Batrakou DG, Randles KN, Morris GE, Harrison DJ, Bickmore WA, Schirmer EC (2013) Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery. Genome Biol 14(2):R14. doi:10.1186/gb-2013-14-2-r14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zullo JM, Demarco IA, Pique-Regi R, Gaffney DJ, Epstein CB, Spooner CJ, Luperchio TR, Bernstein BE, Pritchard JK, Reddy KL, Singh H (2012) DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina. Cell 149(7):1474–1487. doi:10.1016/j.cell.2012.04.035

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Work in the Misteli laboratory is supported by the Intramural Research Program of the National Institutes of Health (NIH), NCI, Center for Cancer Research. KM and BB are supported by Department of Defense Idea Awards (W81XWH-12-1-0224 and W81XWH-12-1-0295).

Author information

Authors and Affiliations

  1. National Cancer Institute, NIH, Bethesda, MD, 20892, USA

    Karen J. Meaburn, Bharat Burman & Tom Misteli

  2. Program in Cell, Molecular and Developmental Biology, Sackler School of Biomedical Sciences, Tufts University, Boston, MA, USA

    Bharat Burman

Authors
  1. Karen J. Meaburn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bharat Burman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tom Misteli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Karen J. Meaburn or Tom Misteli .

Editor information

Editors and Affiliations

  1. Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

    David P. Bazett-Jones

  2. Dalhousie University, Halifax, Nova Scotia, Canada

    Graham Dellaire

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Meaburn, K.J., Burman, B., Misteli, T. (2016). Spatial Genome Organization and Disease. In: Bazett-Jones, D., Dellaire, G. (eds) The Functional Nucleus. Springer, Cham. https://doi.org/10.1007/978-3-319-38882-3_5

Download citation

Publish with us

Policies and ethics

Search

Navigation